BACKGROUND OF THE INVENTION Currently, the conventional practice in performing coronary artery bypass graft procedures on the heart of a patient is to open the chest by making a longitudinal incision along the sternum (e. g., a partial or median sternotomy), placing the patient on a cardiopulmonary bypass (CPB) (heart-lung) machine, stopping the heart from beating by administering a conventional cardioplegia solution (e. g., a potassium chloride solution) to the heart, and then attaching the coronary artery bypass graft (s) to the coronary arteries (and/or aorta in the case of the proximal end of a free graft vessel). The heart-lung machine is needed to maintain the blood circulation through the patient and to provide gas and heat exchange surfaces. However, there are numerous complications associated with conventional open-chest procedures, many of which are related to the use of a heart-lung machine. The use of a heart-lung machine has been shown to be the cause of many of the complications that have been reported in conventional coronary artery bypass graft procedures, such as complement and neutrophil activation, adverse neuropsychologic effects, coagulopathy, and even stroke. The period of CPB should be minimized, if not avoided altogether, to reduce patient morbidity.

A current trend in coronary artery bypass graft surgery is to utilize a minimally invasive surgical technique. Minimally invasive techniques (i. e., surgical techniques that avoid the partial or median sternotomy and/or the use of CPB) have been developed to attempt to reduce or eliminate some of the more serious complications of conventional open-chest cardiac surgery techniques, such as the morbidity associated with the use of CPB. One approach to minimally invasive cardiac surgery is an endoscopic procedure in which access to the heart is gained through several small openings, or ports, in the chest

wall of a patient. The endoscopic method allows surgeons to stop the heart without cracking the chest by utilizing a series of internal catheters to stop blood flow through the aorta and to administer a conventional cardioplegia solution (e. g., a potassium chloride solution) to facilitate stopping the heart. The cardioplegia solution paralyzes the electrical activity of the heart and renders the heart substantially totally motionless during the surgery. The endoscopic approach utilizes groin cannulation to establish cardiopulmonary bypass (CPB) which takes over the function of the heart and lungs by circulating oxygenated blood throughout the body. After CPB is started, an intraaortic balloon catheter that functions as an internal aortic clamp by means of an expandable balloon at its distal end is used to occlude blood flow in the ascending aorta from within. A full description of an example of one preferred endoscopic technique is found in United States Patent No. 5,752,733, the complete disclosure of which is incorporated by reference herein.

A primary drawback of endoscopic cardiac surgery procedures, however, is that such procedures do not avoid the damaging effects of CPB. CPB has been shown to be the cause of many of the complications that have been reported in conventional coronary artery bypass graft procedures, such as stroke. The period of cardiopulmonary bypass should be minimized, if not avoided altogether, to reduce patient morbidity.

An approach to minimally invasive cardiac surgery that avoids CPB is minimally invasive direct coronary artery bypass grafting (MIDCAB) on a beating heart. Using this method, the heart typically is accessed through a mini-thoracotomy (i. e., a 6 to 8 cm incision in the patient's chest) which also avoids the sternal splitting incision of conventional cardiac surgery. The heart may also be accessed through a partial or median sternotomy in an off-pump coronary artery bypass graft (OPCAB) technique which gives the surgeon greater direct access to the heart. In both the MIDCAB and OPCAB procedures, the anastomosis procedure is then performed under direct vision on the beating heart without the use of CPB or potassium chloride cardioplegia. However, there are many obstacles to precise coronary anastomosis during MIDCAB or OPCAB on a beating heart.

In particular, the constant translational motion of the heart and bleeding from the opening in the coronary artery hinder precise suture placement in the often tiny coronary vessel.

In response to problems associated with the above-described minimally invasive surgical techniques, a new minimally invasive surgical platform known as the Transarrest platform has been developed to minimize the cardiac motion of the beating heart while avoiding the need for CPB, aortic cross-clamping and conventional cardioplegia. The

wall of a patient. The endoscopic method allows surgeons to stop the heart without cracking the chest by utilizing a series of internal catheters to stop blood flow through the aorta and to administer a conventional cardioplegia solution (e. g., a potassium chloride solution) to facilitate stopping the heart. The cardioplegia solution paralyzes the electrical activity of the heart and renders the heart substantially totally motionless during the surgery. The endoscopic approach utilizes groin cannulation to establish cardiopulmonary bypass (CPB) which takes over the function of the heart and lungs by circulating oxygenated blood throughout the body. After CPB is started, an intraaortic balloon catheter that functions as an internal aortic clamp by means of an expandable balloon at its distal end is used to occlude blood flow in the ascending aorta from within. A full description of an example of one preferred endoscopic technique is found in United States Patent No. 5,752,733, the complete disclosure of which is incorporated by reference herein.

A primary drawback of endoscopic cardiac surgery procedures, however, is that such procedures do not avoid the damaging effects of CPB. CPB has been shown to be the cause of many of the complications that have been reported in conventional coronary artery bypass graft procedures, such as stroke. The period of cardiopulmonary bypass should be minimized, if not avoided altogether, to reduce patient morbidity.

An approach to minimally invasive cardiac surgery that avoids CPB is minimally invasive direct coronary artery bypass grafting (MIDCAB) on a beating heart. Using this method, the heart typically is accessed through a mini-thoracotomy (i. e., a 6 to 8 cm incision in the patient's chest) which also avoids the sternal splitting incision of conventional cardiac surgery. The heart may also be accessed through a partial or median sternotomy in an off-pump coronary artery bypass graft (OPCAB) technique which gives the surgeon greater direct access to the heart. In both the MIDCAB and OPCAB procedures, the anastomosis procedure is then performed under direct vision on the beating heart without the use of CPB or potassium chloride cardioplegia. However, there are many obstacles to precise coronary anastomosis during MIDCAB or OPCAB on a beating heart.

In particular, the constant translational motion of the heart and bleeding from the opening in the coronary artery hinder precise suture placement in the often tiny coronary vessel.

In response to problems associated with the above-described minimally invasive surgical techniques, a new minimally invasive surgical platform known as the Transarrest platform has been developed to minimize the cardiac motion of the beating heart while avoiding the need for CPB, aortic cross-clamping and conventional cardioplegia. The

Transarrest platform employs a novel pharmaceutical approach to stabilizing the heart.

This revolutionary pharmaceutical approach to cardiac stabilization is fully described in co- pending nonprovisional patent application for Compositions, Apparatus and Methods For Facilitating Surgical Procedures, Serial No. 09/131,075, filed August 7,1998, and invented by Francis G. Duhaylongsod, M. D, the entire contents of which are expressly incorporated by reference herein. As described therein, pharmaceutical compositions, devices, and methods are provided which are useful for medical and surgical procedures which require precise control of cardiac contraction, such as minimally invasive CABG procedures.

Generally, the Transarrest platform involves the administration of a novel cardioplegia solution which provides for precise heart rate and rhythm control management while maintaining the ability of the heart to be electrically paced (i. e., which does not paralyze the electrical activity of the heart as with conventional cardioplegia solutions).

Specifically, the novel cardioplegia solution comprises a pharmaceutical composition which is capable of inducing reversible ventricular asystole in the heart of a patient, while maintaining the ability of the heart to be electrically paced."Reversible ventricular asystole"refers to a state wherein autonomous electrical conduction and escape rhythms in the ventricle are suppressed. A state of the heart may be induced wherein the heart is temporarily slowed to at least about 25 beats per minute or less, and often about 12 beats per minute or less. The induced ventricular asystole is reversible and after reversal, the heart functions are restored, and the heart is capable of continuing autonomous function.

The pharmaceutical composition may preferably include, for example, an atrioventricular ("AV") node blocker and a beta blocker. As used herein, the term"AV node blocker"refers to a compound capable of reversibly suppressing autonomous electrical conduction at the AV node, while still allowing the heart to be electrically paced to maintain cardiac output. Preferably, the AV node blocker, or the composition comprising the AV node blocker, reduces or blocks ventricular escape beats and cardiac impulse transmission at the AV node of the heart, while the effect on depolarization of the pacemaker cells of the heart is minimal or nonexistent. The beta blocker is provided in one embodiment in an amount sufficient to substantially reduce the amount of AV node blocker required to induce ventricular asystole. For example, the AV node blocker may be present in the composition in an amount which is 50% or less by weight, or optionally about 1 to

Transarrest platform employs a novel pharmaceutical approach to stabilizing the heart.

This revolutionary pharmaceutical approach to cardiac stabilization is fully described in co- pending nonprovisional patent application for Compositions, Apparatus and Methods For Facilitating Surgical Procedures, Serial No. 09/131,075, filed August 7,1998, and invented by Francis G. Duhaylongsod, M. D, the entire contents of which are expressly incorporated by reference herein. As described therein, pharmaceutical compositions, devices, and methods are provided which are useful for medical and surgical procedures which require precise control of cardiac contraction, such as minimally invasive CABG procedures.

Generally, the Transarrest platform involves the administration of a novel cardioplegia solution which provides for precise heart rate and rhythm control management while maintaining the ability of the heart to be electrically paced (i. e., which does not paralyze the electrical activity of the heart as with conventional cardioplegia solutions).

Specifically, the novel cardioplegia solution comprises a pharmaceutical composition which is capable of inducing reversible ventricular asystole in the heart of a patient, while maintaining the ability of the heart to be electrically paced."Reversible ventricular asystole"refers to a state wherein autonomous electrical conduction and escape rhythms in the ventricle are suppressed. A state of the heart may be induced wherein the heart is temporarily slowed to at least about 25 beats per minute or less, and often about 12 beats per minute or less. The induced ventricular asystole is reversible and after reversal, the heart functions are restored, and the heart is capable of continuing autonomous function.

The pharmaceutical composition may preferably include, for example, an atrioventricular ("AV") node blocker and a beta blocker. As used herein, the term"AV node blocker"refers to a compound capable of reversibly suppressing autonomous electrical conduction at the AV node, while still allowing the heart to be electrically paced to maintain cardiac output. Preferably, the AV node blocker, or the composition comprising the AV node blocker, reduces or blocks ventricular escape beats and cardiac impulse transmission at the AV node of the heart, while the effect on depolarization of the pacemaker cells of the heart is minimal or nonexistent. The beta blocker is provided in one embodiment in an amount sufficient to substantially reduce the amount of AV node blocker required to induce ventricular asystole. For example, the AV node blocker may be present in the composition in an amount which is 50% or less by weight, or optionally about 1 to

20% by weight of the amount of AV node blocker alone required to induce ventricular asystole.

The pharmaceutical composition, such as an AV node blocker, capable of causing ventricular asystole in a preferred embodiment is a cholingeric agent such as carbachol, although other cholingeric agents may be used as well such as acetylcholine, methacholine, bethanechol, arecoline, norarecoline, neostigmine, pyridostigmine, and other agents that increase cyclic GMP levels by direct or indirect cholinergic receptor stimulation. Other exemplary AV node blockers include calcium channel blockers, adenosine A I receptor agonists, adenosine deaminase inhibitors, cholinesterase inhibitors, monamine oxidase inhibitors, serotoninergic agonists, antiarrythmics, cardiac glycosides, and local anesthetics.

Examples of these AV node blockers include verapamil, diltiazem, lidocaine, procaine, procainamide, quinidine, choloroquine, amiodarone, pilocarpine, ethmozine, propafenone, flecainide, encainide, tranylcypromine, serotonin, adenosine, digoxin, digitalis, dipyridamole, ibutilide, zapranest, sotalol, metoclopromide and combinations thereof.

In the preferred embodiment, the beta blocker is propranolol, although other suitable beta blockers may be used as well. Other exemplary beta blockers include atenolol, acebutolol, labetalol, metoprolol, nadolol, oxprenolol, penbutolol, pindolol, sotalol and timolol, and any combinations or pharmaceutically acceptable salts thereof.

Alternatively, celiprolol, betaxolol, bevantolol, bisoprolol, esmolol, alprenolol, carterolol, or teratolol may be used. The beta blocker may be any naturally occurring or synthetic analogue capable of blocking beta-adrenergic receptor sites. The administration of the beta blocker is preferably prior to, or contemporaneously with, the administration of the cholinergic agent, and results in a synergistic effect between the beta blocker and the cholinergic agent. The use of a cholinergic agent, such as carbachol, in combination with a beta-blocker, such as propranolol, produces ventricular asystole at significantly reduced dosages of the cholinergic agent, while maintaining a short half-life and rapid onset of effect.

In one embodiment to induce reversible ventricular asystole in a patient, the beta- blocker propranolol and the AV node blocker carbachol are serially administered in an initial intracoronary bolus to induce reversible ventricular asystole of the heart, and then carbachol is administered as a periodic or continuous intracoronary infusion to maintain ventricular asystole during the course of the surgical procedure. For example, an intracoronary injection of about 0.5 to 4 mg, for example about 1 mg, of propranolol is

20% by weight of the amount of AV node blocker alone required to induce ventricular asystole.

The pharmaceutical composition, such as an AV node blocker, capable of causing ventricular asystole in a preferred embodiment is a cholingeric agent such as carbachol, although other cholingeric agents may be used as well such as acetylcholine, methacholine, bethanechol, arecoline, norarecoline, neostigmine, pyridostigmine, and other agents that increase cyclic GMP levels by direct or indirect cholinergic receptor stimulation. Other exemplary AV node blockers include calcium channel blockers, adenosine A I receptor agonists, adenosine deaminase inhibitors, cholinesterase inhibitors, monamine oxidase inhibitors, serotoninergic agonists, antiarrythmics, cardiac glycosides, and local anesthetics.

Examples of these AV node blockers include verapamil, diltiazem, lidocaine, procaine, procainamide, quinidine, choloroquine, amiodarone, pilocarpine, ethmozine, propafenone, flecainide, encainide, tranylcypromine, serotonin, adenosine, digoxin, digitalis, dipyridamole, ibutilide, zapranest, sotalol, metoclopromide and combinations thereof.

In the preferred embodiment, the beta blocker is propranolol, although other suitable beta blockers may be used as well. Other exemplary beta blockers include atenolol, acebutolol, labetalol, metoprolol, nadolol, oxprenolol, penbutolol, pindolol, sotalol and timolol, and any combinations or pharmaceutically acceptable salts thereof.

Alternatively, celiprolol, betaxolol, bevantolol, bisoprolol, esmolol, alprenolol, carterolol, or teratolol may be used. The beta blocker may be any naturally occurring or synthetic analogue capable of blocking beta-adrenergic receptor sites. The administration of the beta blocker is preferably prior to, or contemporaneously with, the administration of the cholinergic agent, and results in a synergistic effect between the beta blocker and the cholinergic agent. The use of a cholinergic agent, such as carbachol, in combination with a beta-blocker, such as propranolol, produces ventricular asystole at significantly reduced dosages of the cholinergic agent, while maintaining a short half-life and rapid onset of effect.

In one embodiment to induce reversible ventricular asystole in a patient, the beta- blocker propranolol and the AV node blocker carbachol are serially administered in an initial intracoronary bolus to induce reversible ventricular asystole of the heart, and then carbachol is administered as a periodic or continuous intracoronary infusion to maintain ventricular asystole during the course of the surgical procedure. For example, an intracoronary injection of about 0.5 to 4 mg, for example about 1 mg, of propranolol is

administered by intracoronary infusion over a time period of about 0.5 to 3.0 minutes, e. g., about 1 minute, preferably followed by a saline flush, such as 2 mL saline flush. This is followed by an intracoronary bolus injection of about 0.01 to 0.5 mg, e. g., about 0.025 to 0.3 mg, e. g., about 0.1 mg carbachol administered over about 0.5 to 3.0 minutes, e. g., about 1 minute, to initially induce ventricular asystole. To maintain ventricular asystole, carbachol is administered as one or more periodic bolus infusions (e. g., about 0.05 mg/bolus) or as an intracoronary infusion at a rate of about 0.01 to 0.3 mg/min, e. g., about 0.025 to 0.3 mg/min, for example, about 0.01 to 0.1 mg/min, e. g., about 0.05 to 0.1 mg/min, e. g., about 0.0825 mg/min, for a time period of about 5 to 90 minutes, preferably about 30 to 90 minutes, depending on the length of the procedure. A dosage amount of about 1.0 mg of phenylephrine or lavofed may be administered to control the hypotensive effects associated with carbachol administration. In most situations, atropine (about 1 mg) is used to reverse ventricular asystole and restore the heart to its normal function.

Electrical pacing wires are connected to the right ventricle and/or left ventricle and/or atria and are used to pace the heart using a novel foot-actuated pacer control system to maintain the patient's blood circulation during the periods in which the surgeon is temporarily not performing the surgical procedure. Thus, for example, in a coronary artery bypass graft procedure, the surgeon can control the pacing of the heart with a convenient foot pedal and can controllably stop the heart as sutures are placed in the vessel walls. The pharmaceutical compositions, devices and methods for drug delivery, and systems for pacing the heart, give a surgeon complete control of the beating heart. The Transarrest procedure described above can be used to facilitate any surgical procedure within the thoracic cavity or other body cavity which requires intermittent stoppage of the heart, reduced oxygen consumption or elimination of movements caused by pulsatile blood flow, whether access is gained to the body cavity via a partial or median sternotomy incision, via a mini-thoracotomy incision, or via one or more small incisions or ports in the chest wall.

In the above-described embodiment of the co-pending Transarrest patent application, the pharmaceutical composition is delivered locally to the AV node of the heart upon which it acts via the AV node artery of the heart. Preferably, the composition is delivered in an antegrade fashion (direction which is the normal direction of blood flow) to the right coronary artery which feeds blood to the AV node artery. In a majority of patients, the right coronary artery is the main vessel supplying blood to the right side of the

heart and to the AV node. However, where the right coronary artery is substantially totally occluded, and in a small subset of about 20% of patients, the 15'septal branch of the left anterior descending artery (which originates from the left coronary artery) may be the vessel which delivers blood to the AV node and can be selected as the delivery conduit for delivering the pharmaceutical composition to the AV node. Additionally, other possible routes of administration to the AV node may include Kugel's artery and the right superior descending artery. Moreover, in certain situations, the pharmaceutical composition can be delivered in a retrograde manner (direction which is opposite to the normal blood flow direction) through a coronary vein, such as the right or left coronary vein, to the AV node.

Typically, the pharmaceutical composition is delivered to the right coronary artery (or left coronary artery) at a location near the bifurcation to the AV node artery and proximal to the right coronary artery's bifurcation into the posterior descending artery by any one of a number of drug delivery means. For example, one method to accomplish this drug delivery is to have an interventional cardiologist place the distal end of a drug delivery catheter within the right (or left) coronary artery via the femoral artery, or other peripheral artery, using standard fluoroscopic techniques. Catheters such as intravascular catheters which are well known for use in diagnostic and therapeutic procedures can be used to administer the drug composition to the cardiovascular system, such as a standard Target Therapeutics Trackerz (Boston Scientific) or Ultrafuse-X (Scimed Corporation) infusion catheter. Additionally, guide catheters are a well known form of catheter used to assist in the introduction of other catheters, guidewires and/or fluids to the arteriovenous system of a patient and can be used to facilitate proper catheter placement or drug delivery into the ostium of a coronary artery. Such guide catheters typically are also designed specifically for percutaneous or surgical (cut-down) insertion through a femoral artery (or other peripheral vessel) in the groin area of the patient and advanced into the cardiovascular system with the aid of x-ray fluoroscopy. Examples of such guide catheters are numerous with a few being disclosed in Pande U. S. Patent No. 4,596,563 and Macaulay et al. U. S.

Patent No. 5,234,416.

While the use of intravascular drug delivery catheters and/or guide catheters has been shown in animal and ongoing human clinical studies to be an effective approach to administering the Transarrest pharmaceuticals to the cardiovascular system, the reliance of this drug delivery approach on fluoroscopy for proper catheter placement through the

tortuous coronary vasculature system has its drawbacks. For example, the use of fluoroscopy is expensive, has potential adverse toxic effects on patients and doctors exposed to it if proper precautions are not taken to prevent exposure to fluoroscopic radiation, and typically is not available in the majority of operating room suites.

Additionally, the cardiac surgeons performing the complex cardiac surgical procedures on the heart, great vessels and/or other internal organs using the Transarrest procedure, for example, typically are not well trained in fluoroscopic techniques, and thus require the assistance of a cardiologist or other trained expert to place the drug delivery catheter in a fluoroscopically equipped cardiology lab prior to the procedure, which adds to the time, expense and complexity of the procedure.

Thus, it would be advantageous to provide a drug delivery system and associated devices that can be placed surgically by a surgeon without the use of x-ray fluoroscopy.

The drug delivery system preferably should include one or more devices that can be easily placed by a surgeon into the thoracic cavity of a patient who may or may not be on CPB and while the heart is beating.

One novel approach to drug delivery that avoids the use of fluoroscopy is to place an infusion or guide catheter into the ostium of a coronary vessel, such as the right coronary artery, through an opening in the aorta. Such a system is fully described in co- pending patent application Serial No. 09/196,636 for"Fluid Delivery Apparatus and Methods", the entire contents of which are expressly incorporated by reference herein. As described therein, an infusion and/or guide catheter is disclosed which is adapted to be introduced into a coronary ostium of a coronary artery of a heart of a patient through an opening in an aorta of the patient, without the aid of fluoroscopic guidance, for delivery of a fluid, such as a cardioplegia solution, or passage of a catheter, into the coronary artery while still permitting blood perfusion from the aorta into the ostium. For example, in one embodiment, the infusion catheter generally comprises a tube having at least one lumen, a proximal end, and a distal end, the tube having at least one bend to facilitate placement of the distal end of the tube into the ostium of the coronary artery when the proximal end of the tube extends from the opening in the aorta, wherein the distal end of the tube is configured to fit within the coronary ostium while still permitting blood perfusion from the aorta into the ostium. The infusion catheter can be used as a system in conjunction with an intravascular catheter, an intraluminal shunt or similar drug delivery device which can be

inserted directly into a coronary vessel, such as the right or left coronary artery, following cardioplegia administration through the infusion catheter.

However, in lieu of the above drug delivery techniques, an additional drug delivery apparatus and method is needed for surgeons who may not desire to reach the coronary artery through an opening in the aorta or through a peripheral access site. One novel drug delivery approach is to deliver the pharmaceutical composition directly into the coronary artery by a direct injection surgical technique.

Several devices have been developed and are known for site-specific drug delivery to within a vascular wall, such as an arterial wall, to assist in the treatment of vascular diseases, including vessel restenosis following percutaneous transluminal coronary angioplasty (PTCA). The majority of these devices require fluoroscopic techniques to advance and position the device within the patient's vasculature system. For example, these site-specific drug delivery systems include intravascular, fluoroscopic devices for site-specific (coronary artery) drug delivery comprising double-balloon catheters, porous balloon catheters, balloon-over-stent catheters, and stent devices, for example. Epicardial drug delivery devices requiring surgical implementation have been developed which include drug-eluting polymer matrices and transpericardial patch devices. Intramural injection of drug-eluting mircroparticles has been used as a drug delivery strategy following angioplasty. See, e. g., "Direct Intraarterial Wall Injection of Microparticles Via a Catheter A Potential Drug Delivery Strategy Following Angioplasty,"Wilensky R., et al., AMER. HEART J., 122: 1136,1991. Intrapericardial injection of drugs has also been used for the treatment of malignant or loculated pericardial effusions in man. See, e. g., Igo et al. U. S. Patent No. 5,634,895. Pharmacological stabilization of the heart to facilitate coronary artery bypass graft procedures, for example, has been achieved (with limited success) by direct needle injection of lignocaine into the intraventricular septum of the heart. See Khanna and Cullen,"Coronary Artery Surgery with Induced Temporary Asystole and Intermittent Ventricular Pacing : An Experimental Study," CARDIOVASCULAR SURGERY, 1996; 4 (2): 231-236. Intraluminal shunts have been placed directly into coronary arteries, specifically the left anterior descending artery, to provide direct blood perfusion of the distal arterial lumen during the construction of coronary artery bypass grafts in a beating heart, such as the Rivetti-LevinsonTM Intraluminal Shunt (Heyer Schulte, Wisconsin). These shunt devices, however, are

difficult to accurately place in a coronary vessel on a beating heart due to the constant translational motion of the vessel.

Intravascular catheters, such as intravenous (IV) and intraarterial catheters, are another well known form of catheter used for fluid or drug delivery directly into a vessel, usually from a peripheral access point such as through the skin of a patient. These intravascular catheters generally comprise a flexible small diameter tube that is inserted into a patient's blood vessel to allow withdrawal or addition of fluid. Typical peripheral IV catheters are used to gain access to a patient's venous system so the patient can be infused with medicaments, IV solutions or other fluids. The proximal end of such a catheter usually includes a hub that is designed to be connected to a fluid supply line or other medical device such as a syringe or a valve or IV pump. The cannula portion of these types of catheters, e. g., the flexible fluid delivery portion at the distal end of the catheter which is configured to be inserted into and to reside within the vessel, is relatively short, e. g., on the order of about one inch long. These peripheral IV catheters are typically placed in one of the patient's veins located in the hand or arm with the hub taped to the patient's skin.

Peripheral IV catheters may also include extension tubes, which are also generally relatively short in length and which extend proximally from the proximal end of the catheter generally coaxial with the cannula and which include a hub at the proximal end.

Examples of typical IV catheters are disclosed, for example, in Bujan U. S. Patent No.

3,064,648, Loper et al. U. S. Patent No. 3,589,361, Monestere U. S. Patent No. 3,851,647, Moorehead U. S. Patent No. 4,177,809, Harms et al. U. S. Patent No. 4,194,504, and Musgrave et al. U. S. Patent No. 5,807,342.

Intraarterial catheters are another form of intravascular catheter that are specifically adapted to be inserted into an artery. Because arteries are normally located deeper in the patient's tissue relative to the patient's skin than are veins, the cannula portion of an arterial catheter is normally longer than the corresponding cannula portion of IV catheters. Arterial catheters are typically used for blood pressure monitoring within an artery, as an introducer for other fluid delivery lines, and for other similar uses. Similar to IV catheters, arterial catheters generally comprise a flexible cannula which is adapted to be inserted into the vessel, a catheter hub at the proximal end of the catheter, an extension tube extending coaxially with the cannula, and a retractable needle for making an opening in the vessel sized for insertion of the cannula. Examples of intraarterial catheters can be found, for

example, in Foti U. S. Patent No. 3,565,074, Kreuzer et al. U. S. Patent No. 5,116,323, and Purdy et al. U. S. Patent No. 5,797,882.

None of the previous devices, however, are designed or are particularly well adapted to deliver a fluid or drug directly into a vessel subject to continuous translational motion, such as a coronary vessel on a beating heart. In the insertion and placement of a catheter in a lumen of a vessel which is located in a portion of the body where considerable movement occurs, such as a coronary vessel on a beating heart, it is important to ease as much as possible the movement of the catheter relative to the vessel both during insertion of the catheter and following catheter placement. This is particularly important to prevent trauma to the vessel and to prevent the catheter from inadvertently dislodging from the vessel during the procedure. It is also important to minimize trauma to the vessel from abrasion resulting from continuous movement of the catheter hub, extension tube, and any wings or other support structure on the catheter when the catheter is secured in place to the vessel. Additionally, in the case of placement of the catheter in a coronary artery during performance of a cardiac surgical procedure, for example, it is also preferable to minimize as much as possible the total portion of the catheter which is located within the operative field on the heart to provide the surgeon with a substantially unobstructed surgical field in which to operate. Thus, a device is needed that allows for smooth and reliable insertion directly into a vessel within a patient's vasculature system even during constant translational motion of the vessel, while also minimizing the risk of trauma to the vessel interior lumen during insertion and placement. The present invention satisfies those needs.

SUMMARY OF THE INVENTION The present invention involves novel devices and methods for local, direct delivery of fluids or drugs, such as cardioplegia agents, to a vessel within a patient's vasculature system, such as a coronary vessel on a beating (non-arrested) heart of a patient, to facilitate cardiac and other surgical procedures. In particular, the invention facilitates surgical delivery of a cardioplegia agent to the coronary vasculature of the heart in the absence of fluoroscopic or other complex catheter guidance techniques.

According to a first aspect of the present invention, a fluid delivery device of relatively simple construction is disclosed for the direct, local delivery of a fluid or drug into a vessel within a patient's vasculature system which generally comprises an elongate cannula having a proximal end, a distal end, and at least one lumen extending between the

proximal end and the distal end of the cannula; a connector coupled adjacent to the proximal end of the cannula defining at least a first lumen and a second lumen, wherein at least the first lumen extends coaxially with and is in fluid communication with the lumen of the cannula; an insertion needle having a sharp distal end, the needle being movably disposed lengthwise in the first lumen and the lumen of the cannula; and a flexible elongate tubular body having a proximal end and a distal end, the distal end of the tubular body being operatively coupled to and in fluid communication with the connector second lumen.

The elongate tubular body preferably has a sufficient length and flexibility to extend outside of the patient when the cannula is at least partially inserted into the vessel.

According to another aspect of the present invention, a fluid delivery device is disclosed for the local, direct delivery of a fluid or drug into a vessel within a patient's vasculature system which generally comprises a support member having a proximal end portion and a distal end portion, and a fluid delivery member axially movably coupled to the support member, the fluid delivery member having a fluid delivery portion and being axially moveable relative to the support member between a first position in which the fluid delivery portion extends outside of the vessel, and at least one second position in which the fluid delivery portion is adapted to be inserted into the vessel through an opening in the vessel. The support member supports the fluid delivery member in its first position and preferably is configured to stabilize a tissue surface on or near the vessel to facilitate insertion of the fluid delivery member (or a portion thereof) into the vessel. The configuration of the support member and the fluid delivery member can take many forms.

For example, in one embodiment, the support member includes a stabilizing means for retaining the distal end portion of the support member relatively immobile with respect to a surface of the vessel, such as a coronary artery on a beating heart. The support member includes an elongated tubular body to which the fluid delivery member is movably coupled. The wall of the elongated tubular body defines an inner lumen which is adapted to be coupled to a vacuum source for effecting a suction force at a distal end of the tubular body. The support member may also further include at least one tissue contact member coupled to a distal end portion of the tubular body which is shaped to engage a tissue surface on at least one side of the vessel. For example, the fluid delivery device can include two contact members shaped as planar feet which are located in a parallel orientation with respect to each other and which are adapted to engage a tissue surface on either side of the vessel to aid the surgeon in aligning the device with the longitudinal

aspect of the vessel to thereby facilitate insertion of the fluid delivery member into the vessel.

The fluid delivery member may be both slidably and removably coupled to the elongated tubular body so that it can be moved axially relative to the tubular body and removed therefrom to permit fluid infusion into the vessel. In the above-described embodiment of the invention, for example, the fluid delivery member generally comprises a cannula portion, a hub member coupled to the proximal end of the cannula portion, and a needle insertion assembly which is slidably coupled to the cannula portion and the hub member. The hub member is configured to be slidably received within a longitudinal channel extending axially along an external surface of the distal end portion of the elongated tubular body. The hub member is releasably fixed to the channel in the first position of the fluid delivery member and is configured to be moved axially along the length of the tubular body when the stabilizing means holds the fluid delivery device adjacent to or near the surface of the vessel. The needle insertion assembly is used to make a small opening, or incision, in the vessel to permit the cannula portion of the fluid delivery member to be inserted therein for fluid delivery. The hub member further preferably includes a pair of spaced-apart suture wings located on either side of the hub member through which a conventional suture (s) can be tied to secure the fluid delivery member proximate the vessel following removal of the needle insertion assembly from the hub member and separation of the fluid delivery member from the tubular body.

According to a further aspect of the present invention, the support member may include one or more actuator mechanisms which is/are adapted to vary the incident angle and/or to control the depth at which the cannula portion of the fluid delivery member is inserted into the vessel. This may be important to provide the practitioner with greater control over the needle insertion assembly to prevent it from inadvertently piercing through the wall of the target vessel opposite the insertion site during insertion and placement of the cannula portion of the fluid delivery member into the vessel.

In a further alternative embodiment of the invention, the fluid delivery device may also be specially adapted to deliver a fluid or drug to an anastomosis site prior or during the creation of an anastomosis graft. In single or multiple bypass graft procedures, for example, the intended target vessel for fluid or drug administration (such as the right coronary artery) may also have a stenosed region therein which needs to be bypassed to provide blood flow to the distal portion of the vessel and any collateral vessels connected

aspect of the vessel to thereby facilitate insertion of the fluid delivery member into the vessel.

The fluid delivery member may be both slidably and removably coupled to the elongated tubular body so that it can be moved axially relative to the tubular body and removed therefrom to permit fluid infusion into the vessel. In the above-described embodiment of the invention, for example, the fluid delivery member generally comprises a cannula portion, a hub member coupled to the proximal end of the cannula portion, and a needle insertion assembly which is slidably coupled to the cannula portion and the hub member. The hub member is configured to be slidably received within a longitudinal channel extending axially along an external surface of the distal end portion of the elongated tubular body. The hub member is releasably fixed to the channel in the first position of the fluid delivery member and is configured to be moved axially along the length of the tubular body when the stabilizing means holds the fluid delivery device adjacent to or near the surface of the vessel. The needle insertion assembly is used to make a small opening, or incision, in the vessel to permit the cannula portion of the fluid delivery member to be inserted therein for fluid delivery. The hub member further preferably includes a pair of spaced-apart suture wings located on either side of the hub member through which a conventional suture (s) can be tied to secure the fluid delivery member proximate the vessel following removal of the needle insertion assembly from the hub member and separation of the fluid delivery member from the tubular body.

According to a further aspect of the present invention, the support member may include one or more actuator mechanisms which is/are adapted to vary the incident angle and/or to control the depth at which the cannula portion of the fluid delivery member is inserted into the vessel. This may be important to provide the practitioner with greater control over the needle insertion assembly to prevent it from inadvertently piercing through the wall of the target vessel opposite the insertion site during insertion and placement of the cannula portion of the fluid delivery member into the vessel.

In a further alternative embodiment of the invention, the fluid delivery device may also be specially adapted to deliver a fluid or drug to an anastomosis site prior or during the creation of an anastomosis graft. In single or multiple bypass graft procedures, for example, the intended target vessel for fluid or drug administration (such as the right coronary artery) may also have a stenosed region therein which needs to be bypassed to provide blood flow to the distal portion of the vessel and any collateral vessels connected

thereto. It would be advantageous, therefore, to provide a fluid delivery device that can be inserted into the anastomosis site (to avoid multiple punctures in the vessel) and which has a low-profile to provide the surgeon with a clear surgical field in which to perform the anastomosis graft. Although any one of the previous embodiments may be used at the site of an anastomosis, a further alternative embodiment of the invention which is particularly well-adapted to administer a fluid or drug to an anastomosis site in a vessel is disclosed which generally includes a fluid delivery member in the form of an intraluminal shunt-type member which is sized and dimensioned to be conformably and slidably received about an intravascular catheter having an elongated tubular body which acts as a support member to support the shunt. A needle stylet assembly is removably coupled to a central lumen within the elongated tubular body and is used to make an opening, or small puncture, in the vessel wall. Following removal of the needle stylet assembly from the lumen of the tubular body, the tubular body can then be advanced partially into the vessel. A fluid, such as a novel cardioplegia agent (s) which is capable of inducing reversible ventricular asystole of the heart while maintaining the ability of the heart to be electrically paced (for example, an AV node blocker compound and a beta blocker compound), can then be delivered through the lumen to induce ventricular asystole in the heart.

With the heart in controlled ventricular asystole, for example, a larger arteriotomy incision can be made in the stationary vessel around the needle puncture site with a standard scalpel or other appropriate cutting instrument. The shunt-type member can then be moved axially along the external surface of the tubular body and removed therefrom as it is inserted into the motionless coronary vessel. The shunt-type member offers the advantage of providing a blood-free anastomosis area for performing an anastomosis to the target vessel at the site of fluid or drug delivery. The shunt-type member can also be used to administer a fluid or drug, such as a novel cardioplegia solution (e. g., a cholinergic agent solution, e. g., carbachol) to the vessel which is capable of maintaining ventricular asystole during the duration of the surgical procedure (as described above), if necessary. The shunt- type member maintains a relatively low-profile within the vessel and thereby permits the surgeon to perform the anastomosis graft in a substantially unobstructed surgical field. The shunt type-member preferably includes a removable grip portion which can be used to guide the shunt-type member axially along the external surface of the tubular body. The grip portion can include one or more suture holes through which a conventional suture (s) can be tied to secure the shunt-type member proximate the vessel during fluid delivery

thereto. It would be advantageous, therefore, to provide a fluid delivery device that can be inserted into the anastomosis site (to avoid multiple punctures in the vessel) and which has a low-profile to provide the surgeon with a clear surgical field in which to perform the anastomosis graft. Although any one of the previous embodiments may be used at the site of an anastomosis, a further alternative embodiment of the invention which is particularly well-adapted to administer a fluid or drug to an anastomosis site in a vessel is disclosed which generally includes a fluid delivery member in the form of an intraluminal shunt-type member which is sized and dimensioned to be conformably and slidably received about an intravascular catheter having an elongated tubular body which acts as a support member to support the shunt. A needle stylet assembly is removably coupled to a central lumen within the elongated tubular body and is used to make an opening, or small puncture, in the vessel wall. Following removal of the needle stylet assembly from the lumen of the tubular body, the tubular body can then be advanced partially into the vessel. A fluid, such as a novel cardioplegia agent (s) which is capable of inducing reversible ventricular asystole of the heart while maintaining the ability of the heart to be electrically paced (for example, an AV node blocker compound and a beta blocker compound), can then be delivered through the lumen to induce ventricular asystole in the heart.

With the heart in controlled ventricular asystole, for example, a larger arteriotomy incision can be made in the stationary vessel around the needle puncture site with a standard scalpel or other appropriate cutting instrument. The shunt-type member can then be moved axially along the external surface of the tubular body and removed therefrom as it is inserted into the motionless coronary vessel. The shunt-type member offers the advantage of providing a blood-free anastomosis area for performing an anastomosis to the target vessel at the site of fluid or drug delivery. The shunt-type member can also be used to administer a fluid or drug, such as a novel cardioplegia solution (e. g., a cholinergic agent solution, e. g., carbachol) to the vessel which is capable of maintaining ventricular asystole during the duration of the surgical procedure (as described above), if necessary. The shunt- type member maintains a relatively low-profile within the vessel and thereby permits the surgeon to perform the anastomosis graft in a substantially unobstructed surgical field. The shunt type-member preferably includes a removable grip portion which can be used to guide the shunt-type member axially along the external surface of the tubular body. The grip portion can include one or more suture holes through which a conventional suture (s) can be tied to secure the shunt-type member proximate the vessel during fluid delivery

through the lumen of the main tubular body. The grip portion can preferably be removed from the shunt-type member prior to insertion of the shunt-type member into the vessel.

In another aspect of the present invention, several methods for directly delivering a fluid or drug to within a coronary vessel on a beating heart are disclosed which in one representative embodiment generally includes providing a fluid delivery device, stabilizing a tissue surface of the heart proximate to or on the coronary vessel near where an opening in the coronary vessel is to be made, making an opening in the coronary vessel, and delivering a fluid into the coronary vessel through the opening with the fluid delivery device.

The method can include, for example, aligning the distal end portion of the fluid delivery device with the longitudinal aspect of the vessel. In one embodiment, the stabilizing includes retaining a distal end portion of the fluid delivery device in abutting engagement with the surface of the coronary vessel by applying a suction force to the surface of the coronary vessel near the distal end portion. The retaining can also include applying proximal finger pressure on either side of the vessel to minimize its motion. The delivering a fluid can include axially moving a fluid delivery member relative to the device to thereby insert a cannula portion of the fluid delivery member into the vessel. The making an opening in a vessel can include making an opening in a coronary vessel selected from the group consisting of a right coronary artery, a left main coronary artery, a left anterior descending artery, a left circumflex artery, a proximal coronary artery, and any branches thereof. The device may also be used to administer (or withdraw) a fluid from other blood vessels and body organs.

The invention described below solves the deficiencies of the prior art and offers a number of advantages that will be apparent to one of ordinary skill in the art from the following detailed description, accompanying figures, and appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is side elevational view of a first embodiment of a fluid delivery device constructed in accordance with the principles of the present invention.

Figure 2 is a perspective view of the device of Figure 1 being inserted into a right coronary artery on the heart of a patient for its intended application.

Figure 3 is a side elevational view showing the patient's thoracic cavity with the extension tube portion of the fluid delivery device extending outside the thoracic cavity.

Figure 4 is an enlarged perspective view of the heart of the patient of Figures 2 and 3 showing the fluid delivery device being inserted into the right coronary artery.

Figure 5 is a side elevational view of an alternative embodiment of the invention which is particularly well-adapted to administer a fluid or drug to the site of an anastomosis in a coronary vessel (such as the right coronary artery) which generally includes a support member in the form of an intravascular catheter and a fluid delivery member movably coupled to the support member which is in the form of a shunt.

Figure 6 is a perspective view showing the device of Figure 5 being inserted into a right coronary artery of a patient's heart.

Figure 7 is a side-elevational view of the device of Figure 6 prior to removal of the needle insertion assembly therefrom.

Figure 8 is a side-elevational view of the device of Figure 7 following removal of the needle insertion assembly therefrom.

Figure 8A is a detailed, enlarged view of the shunt member of the device of Figure 7 shown secured to a tissue surface of the heart proximate the vessel.

Figure 9 is a side-elevational view of the device of Figure 8A showing an arteriotomy incision being made in the vessel at the fluid delivery device insertion site following removal of the grasping flange from the shunt member.

Figure 10 is a side-elevational view showing the shunt member fully inserted into the vessel following removal of the intravascular catheter portion of the fluid delivery device from the operative site.

Figure 11 is a perspective view of an alternative embodiment of a fluid delivery device constructed in accordance with the principles of the present invention which includes a support member and a fluid delivery member movably coupled thereto, the support member being adapted to stabilize and/or align a region of the vessel near where an opening in the vessel is to be made prior to insertion of the fluid delivery member into the vessel.

Figure 11 A is a side-elevational view of the fluid delivery member which is movably coupled to the fluid delivery device of Figure 11.

Figure 12 is a transverse cross-sectional view of the distal end portion of the support member of the fluid delivery device of Figure 11.

Figure 12A is a bottom-end view of the distal end portion of the support member of the fluid delivery device of Figure 11.

Figure 4 is an enlarged perspective view of the heart of the patient of Figures 2 and 3 showing the fluid delivery device being inserted into the right coronary artery.

Figure 5 is a side elevational view of an alternative embodiment of the invention which is particularly well-adapted to administer a fluid or drug to the site of an anastomosis in a coronary vessel (such as the right coronary artery) which generally includes a support member in the form of an intravascular catheter and a fluid delivery member movably coupled to the support member which is in the form of a shunt.

Figure 6 is a perspective view showing the device of Figure 5 being inserted into a right coronary artery of a patient's heart.

Figure 7 is a side-elevational view of the device of Figure 6 prior to removal of the needle insertion assembly therefrom.

Figure 8 is a side-elevational view of the device of Figure 7 following removal of the needle insertion assembly therefrom.

Figure 8A is a detailed, enlarged view of the shunt member of the device of Figure 7 shown secured to a tissue surface of the heart proximate the vessel.

Figure 9 is a side-elevational view of the device of Figure 8A showing an arteriotomy incision being made in the vessel at the fluid delivery device insertion site following removal of the grasping flange from the shunt member.

Figure 10 is a side-elevational view showing the shunt member fully inserted into the vessel following removal of the intravascular catheter portion of the fluid delivery device from the operative site.

Figure 11 is a perspective view of an alternative embodiment of a fluid delivery device constructed in accordance with the principles of the present invention which includes a support member and a fluid delivery member movably coupled thereto, the support member being adapted to stabilize and/or align a region of the vessel near where an opening in the vessel is to be made prior to insertion of the fluid delivery member into the vessel.

Figure 11 A is a side-elevational view of the fluid delivery member which is movably coupled to the fluid delivery device of Figure 11.

Figure 12 is a transverse cross-sectional view of the distal end portion of the support member of the fluid delivery device of Figure 11.

Figure 12A is a bottom-end view of the distal end portion of the support member of the fluid delivery device of Figure 11.

Figure 13 is a perspective view of the proximal end portion of the support member of the fluid delivery device of Figure 11.

Figure 13A is a transverse cross-sectional view of the proximal end portion of the support member of the fluid delivery device of Figure 11.

Figure 14 is a perspective view of an alternative embodiment of a fluid delivery device constructed in accordance with the principles of the present invention which includes a support member and a fluid delivery member movably coupled thereto, wherein the support member can be manipulated to control the incident angle and the penetration depth at which the fluid delivery member is inserted into the vessel.

Figure 15A is a front-side elevational view of the fluid delivery device of Figure 14.

Figure 15B is a rear-end elevational view of the fluid delivery device of Figure 14.

Figure 15C is a perspective rear-end elevational view of the fluid delivery device of Figure 14.

DETAILED DESCRIPTION OF THE INVENTION The present invention relates generally to apparatus and methods for the direct delivery of fluids or drugs, such as cardioplegia agents, into a vessel within the vasculature system of a patient. The present invention is particularly well suited for directly delivering a cardioplegia agent to within a coronary artery on a beating heart, such as the right coronary artery, during the course of a surgical procedure, such as a coronary artery bypass graft procedure. The devices of the present invention allow a physician to place the devices within a vessel, such as a coronary vessel, without fluoroscopy and with minimal trauma to the vessel endothelium. Although the devices of the present invention are particularly well- adapted for delivery of a fluid or drug to within a vessel subject to constant translational motion, it is to be understood that the devices can be used to administer a fluid or drug into any vessel or other body organ within a patient. In addition, in certain cases, the devices of the present invention can be used to pass an intravascular device into the vessel, such as a stent or a shunt, for example.

For consistency and convenience, throughout the description the two end portions of the fluid delivery apparatus and its various components are referred to as the proximal and distal end portions respectively, the distal end portion being the end portion which is located towards the selected vessel within the patient and the proximal end portion being the opposite end portion which is closest to the user of the device.

Referring to the drawings wherein like numerals indicate like elements, various embodiments of a fluid delivery device for the local, direct injection of fluids or drugs into a vessel within a patient's vasculature system are shown in accordance with the principles of the present invention.

Figure 1 depicts a first embodiment of a fluid delivery device 10 constructed in accordance with the principles of the present invention. The fluid delivery device 10 very generally includes a relatively low-profile cannula portion 20, a soft, atraumatic Y-shaped connector 30 coupled to a proximal end portion of the cannula portion 20, an insertion needle assembly 40 which extends lengthwise through the connector 30 and cannula portion 20, and a flexible extension tube 50 which is fluidly coupled to connector 30 and cannula portion 20. Cannula portion 20 has a single lumen extending therethrough.

However, cannula portion 20 could also include two lumens extending therethrough, a first lumen dedicated for the insertion needle assembly 40 and a separate dedicated lumen fluidly coupled to extension tube 50.

Cannula portion 20 has a length"d"shown in the drawings which preferably tapers slightly towards the distal tip 22 of the cannula portion to facilitate insertion into a selected vessel. The distal tip 22 of cannula portion 20 is preferably smooth and slightly rounded as shown to prevent vessel trauma during device insertion and placement. The cannula portion 20 preferably has a sufficient length and rigidity to extend generally coaxially within a vessel, such as a coronary artery, and to substantially retain its position therein without backing out of the vessel after it is inserted therein. For example, for applications in a coronary vessel on a beating heart, the cannula portion 20 should have a length of at least about 20 mm, preferably between about 20 to 50 mm, and more preferably between about 40 and 50 mm, to adequately maintain its position within the vessel. The cannula portion 20 must also be configured to reside in the vessel, such as a coronary artery, without any significant decrease in the blood flow through the vessel. The coronary arteries are very small and typically have a diameter in the range of between about 1 to 5 mm. Because the coronary vessels are so small, the outside diameter of the cannula portion 20 must also be sufficiently small so as not to cause trauma to the vessel during device insertion and placement and to allow for adequate blood perfusion about the cannula portion 20 after it is inserted into the vessel. The outside diameter of cannula portion 20 thus should be about 1 mm or less. The configuration of the cannula portion 20 can vary depending on the size of the vessel into which it is inserted.

Cannula portion 20 may be formed of polymeric materials such as polyurethane, polyethylene, polyvinylchloride and the like, and any suitable combinations thereof.

Cannula portion 20 can be formed of a hydrophilic polyurethane that softens when exposed to physiological conditions (e. g., about 37° aqueous saline or blood). Cannula portion 20 can also be provided with additional materials to add strength, stiffness and/or flexibility to the cannula portion 20. For example, cannula portion 20 may include a relatively thick- walled braided or wound wire matrix (e. g., made from stainless steel) to provide overall stiffness to the cannula portion 20. By varying the pitch of the braided or wound wire, the steerability of the cannula portion 20 can be modified along its length. The relative thickness of the cannula portion 20 may vary depending on the use of the device and the vessel anatomy into which it is placed.

Connector 30 is fixedly attached to the proximal end of cannula portion 20.

Connector 30 includes two lumens 32 and 34. Lumen 32 extends generally coaxially with and is fluidly coupled to the internal lumen within cannula portion 20. Lumen 32 is sized to releasably receive insertion needle assembly 40 therein. Bonded to the proximal end of lumen 32 is a standard flow control plug, or grommet, 33 which seals the inlet opening to lumen 32 following removal of needle insertion assembly 40. Flow control plug 33 is made from conventional plastic materials such as silicone or latex, preferably silicone, and is preferably located flush with the proximal end of the lumen 32 or may be recessed slightly therefrom. Alternatively, lumen 32 (and/or lumen 34) may be provided with a hemostasis valve member in lieu of flow control plug 33. Any suitable valve member may be employed including a Touhy Borst valve, ball valve, spool valve, poppet valve, diaphragm valve, duck-bill valve, and the like, preferably a Touhy Borst valve. Lumen 34 is also fluidly coupled to the internal lumen within cannula portion 20 and is in fluid communication with a central lumen extending through extension tube 50.

The provision of a Y-shaped connector 30 located immediately adjacent to cannula portion 20 has several advantages. For one, the Y-shaped connector 30 allows extension tube 50 (which among other things provides strain relief for the device 10) to be spaced- apart and separated from insertion needle assembly 40. Thus, insertion needle assembly 40 does not need to be configured to extend along a lengthy extension tube and can be made shorter than is typical for most IV or intraarterial catheters. Further, by locating the insertion needle assembly 40 as close as possible to the vessel insertion site, the practitioner can manipulate it near to the intended target vessel, which is important for surgeons who

are used to manipulating instruments near the operative site typically under the assistance of magnification headwear. This provides the surgeon or surgeon's assistant with greater control over the insertion/removal of the needle insertion assembly 40. Additionally, locating the needle insertion assembly 40 separately from the main extension tube 50 of the device has the advantage of preventing kinking of the extension tube 50 during retraction and removal of the needle thereby facilitating needle retraction.

Connector 30 preferably has a low-profile cross-section which has a generally circular or oval configuration. However, any other low profile shape, such as an elliptical shape or a generally rectangular shape could also be used. The oval configuration avoids sharp corners so that connector 30 minimizes trauma to the heart or vessel when it is secured proximate thereto. The low-profile of connector 30 also ensures that no substantial portion of device 10 substantially obstructs the surgical field in which the surgeon operates, which is particularly important when the device 10 is used to deliver a fluid to a coronary vessel, such as the right coronary artery, at or near the site of an anastomosis. Connector 30 may include one or more suture holes 35 therein which allow the connector to be stably sutured to a tissue surface of the heart proximate the intended target vessel, for example.

Preferably, there is one suture hole 35 on either side of connector 30. In addition, other means to secure the connector 30 proximate the vessel can be employed as well, such as, for example, applying an adhesive to the lower surface of the connector 30, such as cyanoacrylate, e. g., Loctite0, manufactured by Loctite Corporation (Hartford, CT), or other bonding materials. The adhesive is preferably compatible with biological tissue surfaces and the like and should be capable of easily being flaked off of the tissue surface following removal of the connector therefrom. Other adhesives or securing mechanisms, such as tape, could also be used. For example, a self-adhesive backing could be applied to the undersurface of the connector 30 to fix it in place proximate the vessel as described below. Connector 30 may be made from a suitable relatively soft plastic material such as polyurethane and may have a substantially planar bottom surface or a curved bottom surface to conform to the topical surface of the heart, a vessel, or other tissue conformation.

The connector 30, due to its inherent flexibility, preferably can be manipulated to substantially conform to the topical surfaces of the heart to which it is secured.

Alternatively, to improve flexibility, flexible connector 30 could also comprise a laminate structure formed by an upper paper or other woven or non-woven cloth layer, an inner cellulose foam layer, and a bottom adhesive layer. Alternatively, connector 30 may

are used to manipulating instruments near the operative site typically under the assistance of magnification headwear. This provides the surgeon or surgeon's assistant with greater control over the insertion/removal of the needle insertion assembly 40. Additionally, locating the needle insertion assembly 40 separately from the main extension tube 50 of the device has the advantage of preventing kinking of the extension tube 50 during retraction and removal of the needle thereby facilitating needle retraction.

Connector 30 preferably has a low-profile cross-section which has a generally circular or oval configuration. However, any other low profile shape, such as an elliptical shape or a generally rectangular shape could also be used. The oval configuration avoids sharp corners so that connector 30 minimizes trauma to the heart or vessel when it is secured proximate thereto. The low-profile of connector 30 also ensures that no substantial portion of device 10 substantially obstructs the surgical field in which the surgeon operates, which is particularly important when the device 10 is used to deliver a fluid to a coronary vessel, such as the right coronary artery, at or near the site of an anastomosis. Connector 30 may include one or more suture holes 35 therein which allow the connector to be stably sutured to a tissue surface of the heart proximate the intended target vessel, for example.

Preferably, there is one suture hole 35 on either side of connector 30. In addition, other means to secure the connector 30 proximate the vessel can be employed as well, such as, for example, applying an adhesive to the lower surface of the connector 30, such as cyanoacrylate, e. g., Loctite0, manufactured by Loctite Corporation (Hartford, CT), or other bonding materials. The adhesive is preferably compatible with biological tissue surfaces and the like and should be capable of easily being flaked off of the tissue surface following removal of the connector therefrom. Other adhesives or securing mechanisms, such as tape, could also be used. For example, a self-adhesive backing could be applied to the undersurface of the connector 30 to fix it in place proximate the vessel as described below. Connector 30 may be made from a suitable relatively soft plastic material such as polyurethane and may have a substantially planar bottom surface or a curved bottom surface to conform to the topical surface of the heart, a vessel, or other tissue conformation.

The connector 30, due to its inherent flexibility, preferably can be manipulated to substantially conform to the topical surfaces of the heart to which it is secured.

Alternatively, to improve flexibility, flexible connector 30 could also comprise a laminate structure formed by an upper paper or other woven or non-woven cloth layer, an inner cellulose foam layer, and a bottom adhesive layer. Alternatively, connector 30 may

comprise only an adhesive bottom layer and an upper cellulose foam layer. The cyanoacrylate bottom surface of connectro 30 may include a removable backing (e. g., of paper or plastic) covering it before use, which can then be peeled away to expose the adhesive surface. The backing prefereably resists tearing and may be divided into a number of pieces to ease attachement of the connector 30 to the heart.

Insertion needle assembly 40 includes an elongate, non-coring beveled insertion needle 42 having a proximal end portion 44, a distal end portion 46 and a central hollow bore passageway therethrough. Insertion needle 42 is sized to fit within and to extend coaxially with lumen 32 of connector 30 and the central lumen through cannula portion 20.

Insertion needle 42 has a clear, transparent hub 48 attached to the proximal end portion 44 of the needle and a sharpened tip 49 at the distal end of the needle 42. Needle 42 has a sufficient length so that sharpened tip 49 of needle 42 is capable of extending beyond the distal tip 22 of cannula portion 20 when insertion needle assembly 40 is disposed within lumen 32 and the lumen through cannula portion 20. The device 10 may also be provided with a shield (not shown) that releasably fits over needle 42 and cannula portion 20 to protect the projecting needle tip 49 of the device 10. Needle hub 48 is preferably formed from a thermoplastic material that is substantially transparent or at least translucent, so that the presence of fluid, such as blood, is visible in the hub. Thermoplastic materials such as polycarbonate, polypropylene, and polyamide are suitable for forming hub 48.

The flexible extension tube 50 includes a proximal end portion 52, a distal end portion 54, and a conventional luer adapter 56 which is configured to easily connect with other fluid carrying members such as a syringe or a valve or IV pump. Extension tube 50 also includes a central lumen therethrough and is formed from a soft, flexible material such as silicone. Extension tube 50 preferably has a sufficient length and flexibility to extend outside of the thoracic cavity (or other applicable body cavity depending on the application) when the cannula portion 20 is inserted into a coronary vessel on the heart, for example. The length of extension tube should be at least about 100 mm or greater, for example between about 125 to 175 mm, for example about 150 mm. The relatively long length of extension tube 50 serves several important functions. For one, the long extension tube 50 provides optimal strain relief to the device 10 to prevent the cannula portion 20 from pulling out of the vessel. The lengthy tubing also allows other fluid delivery members (such as an IV pump and the like) to be coupled to the device 10 far removed from the operative site, which minimizes trauma to the vessel from abrasion resulting from

continuous movement of the extension tube adapter 56, fluid carrying members coupled thereto, and extension tube 50, when the connector 30 is secured in place adjacent to the vessel. The relatively long length of the extension tube 50 also allows the tube to be secured to the chest cavity (or to a surgical retractor placed therein which separates the ribs to provide access to the chest cavity) away from the operative site. This helps to keep the operative field substantially unobstructed providing the surgeon with more space in which to operate. The extension tube 50 may optionally include an anchor 57 (shown in phantom) fixed to the proximal end portion 52, such as an alligator clip for example, or similar fixation member, to removably attach the device 10 to a surgical retractor used to spread the ribs to provide direct access to the thoracic cavity, such as any of the surgical thoracic cavity retractors disclosed in U. S. Patent Nos. 4,726,356,4,829,985, and 5,025,779, the entire contents of which are expressly incorporated by reference herein. Various other fixation devices which are known to those of ordinary skill in the art could also be used in lieu of a clip to secure the tube 50 to a stable support to free the hands of the surgeon or surgeon's assistant during the procedure. Further, the tube 50 may be attached to a fixed support other than a fixture on a retractor system such as the surgical table or the chest cavity of the patient (using one or more purse string sutures, for example).

The device 10 may optionally be provided with a thin wire (not shown) which can be slidably received within the needle bore through needle 42. Thus, needle 42 may be removed over the wire following insertion of the cannula portion 20 partially into the vessel leaving the small wire extending a short distance beyond the distal tip 22 of cannula portion 20. The thin wire can then be extended further into the vessel and can serve as a steering or guiding mechanism to help direct the passage of the cannula portion 20 further into the vessel, if necessary. Further optionally, cannula portion 20 can be provided with some form of illumination capability, such as a small light-emitting diode (LED) located near the distal tip 22 of the cannula portion, to aid the practitioner in visualizing the progress of the cannula portion 20 as it is inserted deeper into the vessel, similar to the techniques for vessel illumination disclosed in copending, commonly-assigned CIP patent application for "Fluid Delivery Apparatus and Methods,"filed on May 14,1999 and bearing Attorney's Docket No. 35353-20010.20. Alternatively, the cannula portion 20 could be illuminated in a variety of other ways, including passing an optical fiber (not shown) through a dedicated lumen in the cannula portion 20 until a light delivery portion of the optical fiber resides near the distal tip 22 of the cannula portion 20. The optical fiber could be illuminated with

a conventional white light source, laser source, or by other similar means from outside the patient to provide a visual indication of the presence of the cannula portion within the vessel. The optical fiber could be secured in place to cannula portion 20 through the use of a Touhy-Borst valve, or similar valve member, coupled to one of the lumens of connector 30 as described above.

Further optionally, cannula portion 20 may also be provided with one or more ring electrodes (not shown) to facilitate positioning of the cannula portion proximate to the AV node artery, for example, similar to the techniques for catheter positioning disclosed in commonly-assigned CIP patent application for"Fluid Delivery Apparatus and Methods," filed on May 14,1999 and bearing Attorney's Docket No. 35353-20010.20. The one or more electrode rings would be used to sense electrical signals generated by a pacemaker node of the heart (such as the AV node or, in some cases, the SA node). The respective electrode rings can be used in conjunction with a conventional EKG machine for endocardial mapping as is known in the art. The one or more ring electrodes can provide the practitioner with a nonvisual indication of where the distal portion of the cannula portion 20 is located with respect to the AV node artery, for example, by monitoring the electrical activity of the AV node. In this way, fluid or drug delivery can be accurately targeted to the region of the vessel which is located proximal the intended target vessel (i. e., the AV node artery) based on the recorded electrical signals of the pacemaker node (e. g., the AV node).

The operation of the device 10 of Figure 1 for inducing reversible ventricular asystole in the heart of a patient to facilitate a cardiac or other surgical procedure will now be described with reference to Figures 2-4. The methods herein described are used in an open chest coronary artery bypass graft surgical procedure where the surgeon gains access to the heart via a partial or median sternotomy by severing the sternum, or a portion of it, along its longitudinal midline to expose the thoracic cavity. A cardioplegia solution, such as a pharmaceutical composition including an AV node blocker and a beta blocker, can then be delivered to the coronary vasculature with the device 10 of the present invention to induce reversible ventricular asystole. However, the methods described herein are illustrative only and in no way limit the variety of procedures in which the apparatus of the present invention can be used. Of course, those of ordinary skill in the art will appreciate that the present invention could also be used in a MIDCAB (or OPCAB) procedure where access is gained to the thoracic cavity through a mini-thoracotomy incision of no more than

about 12 cm in length, and preferably between about 6 and 8 cm in length. The mini- thoracotomy incision may be intercostal or parasternal but is preferably performed intercostally, and preferably on the second, third, fourth or fifth intercostal spaces, and most preferably on the fourth or fifth intercostal spaces.

In addition, while the direct fluid delivery device 10 and related devices of the present invention are particularly well suited to facilitate a Transarrest procedure, as described above and below, the systems and devices are not limited to their use in a Transarrest procedure, and can be used to facilitate any medical or surgical procedure in which it is required to deliver a therapeutic, diagnostic, or other pharmacologic agent into any vessel within a patient's vasculature system. For example, non-limiting uses of fluid delivery device 10 include delivery of contrast media, e. g., radio-opaque agents, into the coronary vasculature for viewing blood vessel anatomy and blood flow characteristics in a target region, such as at an anastomosis site. In addition, fluid delivery device 10 could be used in other situations to locally administer to the coronary vessels of the heart one or more of a wide variety of therapeutically useful pharmacologic agents to prevent thrombus formation, smooth muscle cell proliferation, or inflammatory responses at an anastomosis site or in a stenosed region of a diseased vessel. Examples of such drugs include anti- platelet or anti-thrombus agents (such as Heparin, Hirudin, tPA, Streptokinase, Urokinase, Persantine, Aspirin, etc.), anti-inflammatory agents (such as steroidal and non-steroidal compounds), and anti-proliferative compounds (such as suramin, monoclonal antibodies for growth factors, and equivalents). In addition, other potentially useful drugs can be administered into the coronary vasculature to facilitate healing and reduce the incidence of thrombosis at an anastomosis site, such as immunosuppressant agents, glycosaminoglycans, collagen inhibitors, and endothelial cell growth promoters. The device 10 can also be used to deliver other therapeutic or diagnostic agents to other vessels and/or body organs within a patient and also can be used to pass other intravascular devices into a vessel, such as a stent, for example, or a clotting wire or other therapeutic or diagnostic device.

Referring now to Figures 2,3 and 4, an exemplary use of the device 10 of the present invention for inducing reversible ventricular asystole in the heart during an open chest surgical procedure is presented. The patient undergoing the procedure, such as a coronary artery bypass graft procedure, is prepared according to known techniques for conventional open chest surgery. In this example, the heart 70 and its main vessels are

about 12 cm in length, and preferably between about 6 and 8 cm in length. The mini- thoracotomy incision may be intercostal or parasternal but is preferably performed intercostally, and preferably on the second, third, fourth or fifth intercostal spaces, and most preferably on the fourth or fifth intercostal spaces.

In addition, while the direct fluid delivery device 10 and related devices of the present invention are particularly well suited to facilitate a Transarrest procedure, as described above and below, the systems and devices are not limited to their use in a Transarrest procedure, and can be used to facilitate any medical or surgical procedure in which it is required to deliver a therapeutic, diagnostic, or other pharmacologic agent into any vessel within a patient's vasculature system. For example, non-limiting uses of fluid delivery device 10 include delivery of contrast media, e. g., radio-opaque agents, into the coronary vasculature for viewing blood vessel anatomy and blood flow characteristics in a target region, such as at an anastomosis site. In addition, fluid delivery device 10 could be used in other situations to locally administer to the coronary vessels of the heart one or more of a wide variety of therapeutically useful pharmacologic agents to prevent thrombus formation, smooth muscle cell proliferation, or inflammatory responses at an anastomosis site or in a stenosed region of a diseased vessel. Examples of such drugs include anti- platelet or anti-thrombus agents (such as Heparin, Hirudin, tPA, Streptokinase, Urokinase, Persantine, Aspirin, etc.), anti-inflammatory agents (such as steroidal and non-steroidal compounds), and anti-proliferative compounds (such as suramin, monoclonal antibodies for growth factors, and equivalents). In addition, other potentially useful drugs can be administered into the coronary vasculature to facilitate healing and reduce the incidence of thrombosis at an anastomosis site, such as immunosuppressant agents, glycosaminoglycans, collagen inhibitors, and endothelial cell growth promoters. The device 10 can also be used to deliver other therapeutic or diagnostic agents to other vessels and/or body organs within a patient and also can be used to pass other intravascular devices into a vessel, such as a stent, for example, or a clotting wire or other therapeutic or diagnostic device.

Referring now to Figures 2,3 and 4, an exemplary use of the device 10 of the present invention for inducing reversible ventricular asystole in the heart during an open chest surgical procedure is presented. The patient undergoing the procedure, such as a coronary artery bypass graft procedure, is prepared according to known techniques for conventional open chest surgery. In this example, the heart 70 and its main vessels are

exposed following a median sternotomy. A detailed view of the heart is shown in Figure 4.

Very generally, heart 70 includes aorta 72 which receives blood pumped from the left ventricle and delivers it to the major organs of the body. Communicating with the aorta are coronary ostia 74 and 76 which are the respective inlet openings to the right 75 and left 77 coronary arteries, respectively. The right coronary artery 75 branches at its distal segment into the posterior descending artery 79 and the circumflex branches. The atrioventricular node artery 81 feeds blood to the AV node (not shown for clarity).

Conventional coronary bypass graft procedures require that a source of arterial blood be prepared for subsequent bypass connection to the diseased artery. An arterial graft can be used to provide a source of blood flow, or a free vessel graft may be used and connected at the proximal end to a source of blood flow. Preferably, the source of blood flow is any one of a number of existing arteries that are dissected in preparation for the bypass graft procedure. In many instances, it is preferred to use either the left or right internal mammary artery. In multiple bypass procedures, it may be necessary to use free graft vessels such as the saphenous vein, gastroepiploic artery in the abdomen, and other arteries harvested from the patient's body as well as synthetic graft materials, such as DacronTM or Gore-Tex grafts. If a free graft vessel is used, the upstream end (proximal) of the dissected vessel, which is the arterial blood source, will be secured to the aorta to provide the desired bypass blood flow, and the downstream end (distal) of the dissected vessel will be connected to the target vessel in a distal anastomosis.

With the heart 70 exposed by partial or median sternotomy, the surgeon identifies a target region in the right (or left) coronary artery 75, (77) where drug delivery is to occur.

To facilitate direct access to the target vessel, the surgeon may use one or more purse-string sutures in the pericardial sac placed under the heart to lift and rotate the heart. The selection of the right 75 versus left 77 coronary artery is dependent upon pre-operative angiographic confirmation of the blood supply route to the AV node. As noted above in the Background section, in a majority of patients, the right coronary artery 75 is the main vessel supplying blood to the right side of the heart and to the AV node. However, where the right coronary artery 75 is substantially totally occluded, and in a small subset of about 20% of patients, the 1 S septal branch of the left anterior descending artery (which originates from the left coronary artery 77) may be the vessel which delivers blood to the AV node and can be selected as the delivery conduit for delivering the pharmaceutical composition to the AV node. Additionally, other possible routes of administration to the

AV node may include Kugel's artery and the right superior descending artery. The exact location for fluid delivery along the length of the vessel chosen is dependent on a number of factors, including accessibility of the target site on the vessel, its visibility, and the degree of disease in the vessel (if any). Where the vessel has a stenosed region therein, it is preferable to deliver the drug to a portion of the vessel distal to the stenosis and as close as possible to the right coronary artery's 75 bifurcation to the posterior descending artery 79.

This will ensure that the majority of the drug reaches the AV node artery 81 and does not bypass the AV node artery 81 via the larger posterior descending artery 79 or other collateral vessels. Optimally, where the target vessel is one of the coronary arteries that needs to be bypassed, the surgeon will chose a fluid administration site that is also the location for an anastomosis graft to the artery to minimize the number of vessel punctures.

Following selection of the optimal target location for drug delivery, the surgeon prepares the target location on the right coronary artery 75 by removing fat tissue and the like to expose the external surface of the vessel. With the right coronary artery 75 partially exposed in the target region, the surgeon stabilizes the heart on opposite sides of the vessel by applying proximal finger pressure to the heart surface on either side of the vessel.

Alternatively, conventional mechanical stabilizers, which have planar surfaces designed to atraumatically grip the epicardium surface of the heart, can be used by the surgeon to stabilize the heart region surrounding the vessel, such as the OctopusTM suction stabilizer device from Medtronic (Minneapolis, Minnesota). With the heart region near the vessel so stabilized, the surgeon then makes a small puncture in the vessel with needle insertion assembly 40 until a small backflash of blood is visualized through the needle hub 48. The cannula portion 20 is then advanced a short distance into the artery. With the cannula portion 20 partially in the vessel, the surgeon then removes needle insertion assembly 40 in a generally straight continuous motion to prevent kinking of the cannula portion 20.

Additionally, the surgeon may now thread one or more sutures through the suture hole (s) 35 provided in connector 30 to secure the connector 30 to the heart to prevent substantial movement of cannula portion 20 relative to the vessel.

With the device 10 securely in place in the vessel, the extension tube 50 is grasped by the surgeon or surgeon's assistant and secured to the retractor 60 or similar fixed structure such as the surgical table or chest wall. Alternatively, the extension tube may be secured to the chest cavity using a clip 57 attached to the extension tube or similar fixation mechanism. The adapter hub 56 of extension tube 50 can then be connected to a

conventional fluid carrying member such as an IV pump or syringe for delivery of a fluid or drug to the vessel. In the preferred use of device 10, a liquid containing a cardioplegia solution is directed through the fluid delivery device 10 and into the artery 75. The preferred cardioplegia solution is a pharmaceutical composition which is capable of reversibly inducing ventricular asystole in the heart while maintaining the ability of the heart to be electrically paced. The procedure is fully detailed in"Compositions, Apparatus and Methods For Facilitating Surgical Procedures,"Serial No. 09/131,075, filed August 7, 1998 and invented by Francis G. Duhaylongsod, M. D, the entire contents of which are expressly incorporated by reference herein. For example, in one embodiment, the pharmaceutical composition comprises an AV node blocker compound such as carbachol and a beta blocker compound such as propranolol. The beta-blocker propranolol and the AV node blocker carbachol can be provided as a single kit in separate pharmaceutically acceptable closed carriers and serially administered as an initial intracoronary bolus to induce reversible ventricular asystole of the heart.

For example, in one embodiment, carbachol is provided in a pharmaceutically acceptable carrier suitable for intracoronary administration. The carbachol may be provided in an aqueous carrier, such as water or saline. In the composition, which optionally may be diluted prior to local cardiac administration, the concentration of carbachol may range, for example, from about 0.01 mg/ml to 2.55 mg/ml, e. g., about 0.1 to 1.0 mg/ml. In one embodiment, propranolol may be provided in a separate pharmaceutically acceptable carrier at a concentration of about 0.5 to 6.0 mg/ml, e. g., about 0.5 to 3.0 mg/ml, or about 1.0 to 2.0 mg/ml, or about 1.0 mg/ml.

The bolus injection of propranolol and carbachol can be administered by connecting adapter hub 56 to a standard infusion pump assembly fluidly coupled to the respective compounds and directing the compounds through the assembly into the vessel. For example, in one embodiment, an intracoronary injection of 0.5 to 4 mg, for example about 1 mg, of propranolol is administered by intracoronary infusion over a time period of about 0.5 to 3.0 minutes, e. g., about 1 minute, preferably followed by a saline flush, such as 2 mL saline flush. This is followed by an intracoronary bolus injection of about 0.01 to 0.5 mg, e. g., about 0.025 to 0.3 mg, e. g., about 0.1 mg carbachol administered over about 0.5 to 3.0 minutes, e. g., about 1 minute, to initially induce ventricular asystole in the heart.

To maintain ventricular asystole, for example, a cardioplegia solution is delivered through the device 10 at an infusion rate sufficient to maintain reversible ventricular

asystole by periodic (e. g., one or more bolus infusions) or continuous infusion. In one embodiment, carbachol is administered as a continuous intracoronary infusion through the infusion catheter 10 at a rate of about 0.01 to 0.3 mg/min, e. g., about 0.025 to 0.3 mg/min, for example, about 0.01 to 0.1 mg/min, e. g., about 0.05 to 0.1 mg/min, e. g., about 0.0825 mg/min, for a time period of about 5 to 90 minutes, preferably about 30 to 90 minutes, depending on the length of the procedure. Carbachol can also be administered as a series of bolus injections through device 10 to maintain reversible ventricular asystole. An intravenous dosage of about 1.0 mg of phenylephrine can be systemically administered to the patient to control any hypotensive effects associated with carbachol administration. In most situations, atropine (about 1 mg) is used to reverse ventricular asystole and restore the heart to its normal function following the surgical procedure. Intracoronary nitroglycerine (e. g., about 200 mcg) can also be administered to the heart to counteract any vasoconstrictive effects associated with phenylephrine administration.

With the heart in controlled ventricular asystole, the heart is appropriately prepared for the anastomosis procedure (or other cardiac or other surgical procedure). Electrical pacing wires are connected to the right ventricle and/or left ventricle and/or atria and are used to pace the heart using a novel foot-actuated pacer control system (as fully described in the co-pending Transarrest patent application Serial No. 09/131,075) to maintain the patient's blood circulation during the periods in which the surgeon is temporarily not performing the surgical procedure. Thus, for example, while bypassing the LAD or other appropriate vessel such as the circumflex vessels (or the right or left coronary artery when necessary), the surgeon can control the pacing of the heart with a convenient foot pedal and can controllably stop the heart as sutures are placed in the vessel walls.

The procedures with which the systems and methods of the present invention are useful include coronary bypass surgery (with full or partial sternotomy or thoracotomy), transmyocardial laser revascularization, tachyarrythmia operations such as electrophysiology lab procedures (diagnostic and therapeutic ablation of arryhthmias), imaging procedures of the heart and great vessels such as CAT scan or MRI procedures, percutaneous transluminal coronary angioplasty, placement of stents such as coronary or aortic stents, operations where uncontrollable hemorrhage is present or anticipated or control of significant hemorrhage is required during the surgical procedure (for example, treatment of injuries to the liver, spleen, heart, lungs, or major blood vessels, including iatrogenic and traumatic injuries to such organs or structures), other procedures including

percutaneous aortic aneurysm graft placement, neurosurgical procedures, such as aneurysm repair, and various other procedures that would benefit from the inducement of ventricular asystole, while maintaining the ability of the heart to be electrically paced. The devices and methods of the present invention can also be used to facilitate robotically-assisted minimally invasive surgery such as described in U. S. Patent Nos. 5,792,135; 5,797,900 and 5,807,377, the entire contents of which are incorporated by reference herein. The devices and methods of the present invention provide a convenient mechanism to administer pharmaceutical compositions to the heart to arrest the heart and thereby provide a motionless field in which to operate, whether a surgeon uses conventional surgical techniques or emerging robotically-assisted techniques.

Turning now to Figures 5-10, an alternative embodiment of the invention is shown which is generally indicated with the reference numeral 110. The device 110 is particularly well-suited for directly delivering a fluid or drug, such as the above-described pharmaceutical compounds, to the site of an anastomosis in a coronary vessel, such as the right coronary artery, for example, prior to or during the creation of an anastomosis graft.

In single or multiple bypass graft procedures, for example, the intended target vessel for fluid or drug administration (such as the right coronary artery) may also have a stenosed region therein which needs to be bypassed to provide blood flow to the distal portion of the vessel and any collateral vessels connected thereto. It would be advantageous, therefore, to provide a fluid delivery device that can be inserted into the anastomosis site (to avoid multiple punctures in the vessel) and which has a low-profile to provide the surgeon with a clear surgical field in which to perform the anastomosis graft. Although the previous embodiment can be used to deliver a fluid or drug at an anastomosis site, an alternative embodiment that is specially adapted for that purpose has been developed which has the advantage of coupling an intraluminal shunt-type device to an intravascular catheter to facilitate insertion of the shunt into the vessel and also to perform the duties discussed above in connection with Figures 1-4.

One of the concerns with anastomosis procedures on a beating, unsupported heart is the manifestation of ischemia in the vessel when the vessel becomes partially or totally temporarily occluded during the procedure. Intraluminal shunts have been developed which maintain distal perfusion and prevent ischemia while at the same time protecting the anastomosis from potential suturing errors. See, for example, Rivetti, L. A. M. D. et al.,"An Intraluminal Shunt for Off Pump Coronary Artery Bypass Grafting. Report of 501

Consecutive Cases and Review of the Technique,"presented at: First World Congress of Minimally Invasive Cardiac Surgery Palais de Congres, Paris, France, May 1997.

However, one of the problems with conventional shunt devices is the difficulty of inserting the devices into a moving vessel on the beating heart.

Fluid delivery device 110 solves that problem and provides a convenient mechanism to deliver a fluid or drug into a vessel at the site of an anastomosis. The device 110 comprises an intravascular catheter 111 which includes a flexible, elongate extension tube 112 having proximal and distal end portions 114 and 116, respectively. The proximal end portion 114 of the catheter 111 includes a conventional Y-shaped adapter hub 118.

Adapter hub 118 includes a first arm 120 through which a retractable needle assembly 124 is slidably received. Second arm 121 of Y-shaped adapter 118 is conventional in the medical field for making connections with other fluid carrying tubular members and includes a standard luer fitting 123 which can be used for connecting with fluid infusion tubing, such as IV catheter tubing, and the like for administering a fluid into arm 121.

Needle assembly 124 is conventional, such as is commercially available from Becton-Dickinson (Sandy, Utah) under the trademark name Angio-SetTM, and generally comprises a non-coring, beveled needle, a generally transparent needle hub at its proximal end, and a stainless steel wire (not shown) coupling the needle to the needle hub. A standard flow control plug 125 can be configured to be secured to the proximal end of arm 120 to seal the inlet opening to arm 120 following removal of needle assembly 124 (See Figure 8). Flow control plug 125 is made from conventional plastic or elastomeric materials such as silicone or latex, preferably silicone. In addition, hub 118 can include a clip (not shown), such as an alligator clip for example, or similar fixation member to removably attach the hub 118 to a surgical retractor, or other relatively stationary structure.

Elongated extension tube 112 defines an internal fluid delivery lumen through which a drug or other fluid passes. The fluid delivery lumen extends from adapter hub 118 through tube 112 and through the distal end portion 116 to a distal opening (not shown).

The distal end portion 116 of the catheter includes a fluid delivery portion 115 which has a similar configuration to cannula portion 20 described previously. The intravascular catheter 111 also includes a fluid delivery member 130 which is adapted to be inserted into the vessel through an opening in the vessel following drug administration through extension tube 112 (as will be explained in greater detail below) for subsequent fluid or drug administration into the vessel while also maintaining blood perfusion through the

vessel. Fluid delivery member 130 is in the form of an intraluminal shunt 132. The shunt 132 may be similar to a shunt available from Heyer-Schulte NeuroCare Group (Pleasant Prairie, Wisconsin), such as the Rivetti-LevinsonTM Shunt, for example. The shunt may also be a shunt apparatus such as is disclosed in co-pending and commonly assigned patent application for"Intraluminal Shunt and Methods of Use,"Serial No. 09/034,849, invented by French et al., the entire contents of which are expressly incorporated by reference herein.

Preferably, the shunt 132 generally includes a primary tubular member 134 which is adapted for insertion into the vessel and which is conformably and slidably received about the extension tube 112. The extension tube 112 acts as a support body to support the shunt 132 prior to its insertion into the selected vessel. The primary tubular member 134 defines at least one perfusion lumen defining a perfusion path through the primary tubular member 134 and provides a blood perfusion path within the vessel. The shunt 132 also includes at least one side arm 136 fluidly coupled to the primary tubular member 134. The side arm 136 defines an inner lumen therein in fluid communication with the primary tubular member lumen, thus defining a fluid or drug delivery path into the vessel. A conventional luer adapter 137 is connected at the proximal end of side arm 136 and can be used to connect the shunt 132 to other fluid carrying members. Unlike any known previous embodiments of the shunt, however, the shunt 132 may also include a peel-away grasping flange 138 which can be used by the surgeon to guide the shunt 132 along extension tube 112 and into the vessel during operation of the device and to fixate the shunt relative to elongate tube 112 to prevent its movement during initial fluid administration through the tube 112, as will be explained below in connection with Figures 6-10. Alternatively, shunt 132 may be slidably coupled to tube 112 in a press-fit or interference-fit relationship so that it will retain its position relative to tube 112 during the insertion and placement in the vessel. The grasping flange 138 includes one or more suture holes 139 through which a suture (s) can be passed to secure the shunt 132 proximate the vessel prior to its insertion.

The shunt also preferably includes two spaced-apart occlusion members in the form of bulbous projections 133 which extend about the primary tubular member 134 close to the opposite ends of the primary tubular member 134, respectively. Occlusion members 133 are constructed of any suitable biocompatible material, preferably silicone. Occlusion members 133 help to secure the primary tubular member in the vessel during use of the shunt 132 and to seal the vessel to force blood through the shunt. The occlusion members

vessel. Fluid delivery member 130 is in the form of an intraluminal shunt 132. The shunt 132 may be similar to a shunt available from Heyer-Schulte NeuroCare Group (Pleasant Prairie, Wisconsin), such as the Rivetti-LevinsonTM Shunt, for example. The shunt may also be a shunt apparatus such as is disclosed in co-pending and commonly assigned patent application for"Intraluminal Shunt and Methods of Use,"Serial No. 09/034,849, invented by French et al., the entire contents of which are expressly incorporated by reference herein.

Preferably, the shunt 132 generally includes a primary tubular member 134 which is adapted for insertion into the vessel and which is conformably and slidably received about the extension tube 112. The extension tube 112 acts as a support body to support the shunt 132 prior to its insertion into the selected vessel. The primary tubular member 134 defines at least one perfusion lumen defining a perfusion path through the primary tubular member 134 and provides a blood perfusion path within the vessel. The shunt 132 also includes at least one side arm 136 fluidly coupled to the primary tubular member 134. The side arm 136 defines an inner lumen therein in fluid communication with the primary tubular member lumen, thus defining a fluid or drug delivery path into the vessel. A conventional luer adapter 137 is connected at the proximal end of side arm 136 and can be used to connect the shunt 132 to other fluid carrying members. Unlike any known previous embodiments of the shunt, however, the shunt 132 may also include a peel-away grasping flange 138 which can be used by the surgeon to guide the shunt 132 along extension tube 112 and into the vessel during operation of the device and to fixate the shunt relative to elongate tube 112 to prevent its movement during initial fluid administration through the tube 112, as will be explained below in connection with Figures 6-10. Alternatively, shunt 132 may be slidably coupled to tube 112 in a press-fit or interference-fit relationship so that it will retain its position relative to tube 112 during the insertion and placement in the vessel. The grasping flange 138 includes one or more suture holes 139 through which a suture (s) can be passed to secure the shunt 132 proximate the vessel prior to its insertion.

The shunt also preferably includes two spaced-apart occlusion members in the form of bulbous projections 133 which extend about the primary tubular member 134 close to the opposite ends of the primary tubular member 134, respectively. Occlusion members 133 are constructed of any suitable biocompatible material, preferably silicone. Occlusion members 133 help to secure the primary tubular member in the vessel during use of the shunt 132 and to seal the vessel to force blood through the shunt. The occlusion members

133 also help to dilate and hold open the coronary arteriotomy while also reducing or preventing bleeding into the surgical field.

The operation of device 110 will now be explained with reference to Figures 6-10.

Similar to the previous embodiment, device 110 can be used to facilitate an anastomosis procedure in which a bypass graft vessel, such as an arterial graft (e. g., the left or right internal mammary artery) or a venous graft (such as a saphenous vein), is connected to a coronary artery. The device 110 can be used to facilitate other procedures as well in which a fluid or drug, such as a therapeutic or diagnostic agent, needs to be administered directly, locally to a vessel. Device 110 is particularly well-suited to facilitate a single or multiple bypass graft procedure in which the right (or left) coronary artery (which is typically the site of drug administration in the preferred use of the device to facilitate a TransarrestTM procedure) has a stenosed region which needs to be bypassed.

The patient is prepared for open-chest surgery using the TransarrestTM platform in a similar manner as described above in connection with the previous embodiment of Figures 1-4. Following selection of the optimal target location for drug delivery in the right coronary artery 75 (which preferably corresponds with the location for an anastomosis graft), the surgeon prepares the target location on the right coronary artery 75 by removing fat tissue and the like to expose the external surface of the vessel. With the right coronary artery 75 partially exposed in the target region, the surgeon stabilizes the heart on opposite sides of the vessel by applying proximal finger pressure to the heart surface on either side of the vessel. Mechanical stabilizers may also be used to stabilize a portion of the vessel.

With the heart region near the vessel so stabilized, the surgeon then makes a small puncture in the vessel with needle assembly 124 until a small backflash of blood is visualized through the needle hub. The fluid delivery portion 115 of catheter 111 is then advanced a short distance into the artery 75 as shown in Figure 7. With the fluid delivery portion 115 partially in the vessel, the surgeon then removes needle assembly 124 in a generally straight continuous motion to prevent kinking of the extension tube 112 as illustrated by the arrow in Figure 7. Flow control plug 125 may then be secured to side arm 120 to prevent the flow of blood or other body fluids through the inlet opening to arm 120 as shown in Figure 8. Additionally, the surgeon may also advance shunt 132 distally towards the vessel as illustrated by the distally-pointing arrow in Figure 8 until the shunt 132 is located proximate the vessel. The surgeon may then thread one or more sutures through the suture

133 also help to dilate and hold open the coronary arteriotomy while also reducing or preventing bleeding into the surgical field.

The operation of device 110 will now be explained with reference to Figures 6-10.

Similar to the previous embodiment, device 110 can be used to facilitate an anastomosis procedure in which a bypass graft vessel, such as an arterial graft (e. g., the left or right internal mammary artery) or a venous graft (such as a saphenous vein), is connected to a coronary artery. The device 110 can be used to facilitate other procedures as well in which a fluid or drug, such as a therapeutic or diagnostic agent, needs to be administered directly, locally to a vessel. Device 110 is particularly well-suited to facilitate a single or multiple bypass graft procedure in which the right (or left) coronary artery (which is typically the site of drug administration in the preferred use of the device to facilitate a TransarrestTM procedure) has a stenosed region which needs to be bypassed.

The patient is prepared for open-chest surgery using the TransarrestTM platform in a similar manner as described above in connection with the previous embodiment of Figures 1-4. Following selection of the optimal target location for drug delivery in the right coronary artery 75 (which preferably corresponds with the location for an anastomosis graft), the surgeon prepares the target location on the right coronary artery 75 by removing fat tissue and the like to expose the external surface of the vessel. With the right coronary artery 75 partially exposed in the target region, the surgeon stabilizes the heart on opposite sides of the vessel by applying proximal finger pressure to the heart surface on either side of the vessel. Mechanical stabilizers may also be used to stabilize a portion of the vessel.

With the heart region near the vessel so stabilized, the surgeon then makes a small puncture in the vessel with needle assembly 124 until a small backflash of blood is visualized through the needle hub. The fluid delivery portion 115 of catheter 111 is then advanced a short distance into the artery 75 as shown in Figure 7. With the fluid delivery portion 115 partially in the vessel, the surgeon then removes needle assembly 124 in a generally straight continuous motion to prevent kinking of the extension tube 112 as illustrated by the arrow in Figure 7. Flow control plug 125 may then be secured to side arm 120 to prevent the flow of blood or other body fluids through the inlet opening to arm 120 as shown in Figure 8. Additionally, the surgeon may also advance shunt 132 distally towards the vessel as illustrated by the distally-pointing arrow in Figure 8 until the shunt 132 is located proximate the vessel. The surgeon may then thread one or more sutures through the suture

hole (s) 139 provided in grasping flange 138 to secure the shunt 132 to a surface of the heart proximate the vessel to prevent substantial movement of the shunt relative to the vessel and extension tube 112 as illustrated schematically in Figure 8A.

With the device 110 securely in place in the vessel, the extension tube 112 is grasped by the surgeon or surgeon's assistant and secured to a retractor or similar fixed support structure. Alternatively, the extension tube may be secured to the chest cavity using a clip (not shown) attached to the hub 118 or by using a similar fixation mechanism attached to the hub. The extension tube 112 can then be connected to a conventional fluid carrying member, such as an IV pump or syringe, using adapter hub 118 for delivery of a fluid or drug to the vessel. In the preferred use of device 110, a liquid containing a cardioplegia solution is directed through the tube 112 and into the artery 75 which is capable of reversibly inducing ventricular asystole in the heart while maintaining the ability of the heart to be electrically paced, as described previously.

When the surgeon is ready to graft to the right coronary artery 75, the surgeon enlarges the small needle puncture site in the vessel made by needle assembly 124 with a standard scalpel 150 or other appropriate surgical cutting instrument as shown in Figure 9.

This cutting procedure may be performed while the heart is temporarily arrested under the action of the pharmaceutical agents described above and while the pacer is temporarily de- activated. The surgeon may then cut through the sutures which connect the shunt 132 to the surface of the heart and peel away the grasping flange 138 from the shunt 132, which allows the shunt 132 to be slidably moved axially relative to extension tube 112. This peel- away action is achieved by tearing a thin skin or bridge connecting the flange to the shunt using one's hand, a scalpel, scissors, or other appropriate cutting instrument. The shunt 132 can be moved along extension tube 112 distally towards the vessel by grasping side arm 136 with forceps or a similar device until the shunt is inserted into the artery. This portion of the procedure is preferably performed on a temporarily arrested heart to facilitate insertion of the shunt 132 into the vessel. With the shunt partially within the vessel, the surgeon then removes intravascular catheter 111 from the vessel as illustrated by the proximally-pointing arrow in Figure 9. The shunt 132 is then fully inserted into the vessel (Figure 10). The luer adapter 137 can be used to connect the shunt 132 to IV tubing and the like to continue the administration of the pharmaceutical composition (s) described above (e. g., to deliver into the vessel the one or more periodic bolus infusions of carbachol or the continuous infusion of carbachol) to maintain ventricular asystole of the heart. The

hole (s) 139 provided in grasping flange 138 to secure the shunt 132 to a surface of the heart proximate the vessel to prevent substantial movement of the shunt relative to the vessel and extension tube 112 as illustrated schematically in Figure 8A.

With the device 110 securely in place in the vessel, the extension tube 112 is grasped by the surgeon or surgeon's assistant and secured to a retractor or similar fixed support structure. Alternatively, the extension tube may be secured to the chest cavity using a clip (not shown) attached to the hub 118 or by using a similar fixation mechanism attached to the hub. The extension tube 112 can then be connected to a conventional fluid carrying member, such as an IV pump or syringe, using adapter hub 118 for delivery of a fluid or drug to the vessel. In the preferred use of device 110, a liquid containing a cardioplegia solution is directed through the tube 112 and into the artery 75 which is capable of reversibly inducing ventricular asystole in the heart while maintaining the ability of the heart to be electrically paced, as described previously.

When the surgeon is ready to graft to the right coronary artery 75, the surgeon enlarges the small needle puncture site in the vessel made by needle assembly 124 with a standard scalpel 150 or other appropriate surgical cutting instrument as shown in Figure 9.

This cutting procedure may be performed while the heart is temporarily arrested under the action of the pharmaceutical agents described above and while the pacer is temporarily de- activated. The surgeon may then cut through the sutures which connect the shunt 132 to the surface of the heart and peel away the grasping flange 138 from the shunt 132, which allows the shunt 132 to be slidably moved axially relative to extension tube 112. This peel- away action is achieved by tearing a thin skin or bridge connecting the flange to the shunt using one's hand, a scalpel, scissors, or other appropriate cutting instrument. The shunt 132 can be moved along extension tube 112 distally towards the vessel by grasping side arm 136 with forceps or a similar device until the shunt is inserted into the artery. This portion of the procedure is preferably performed on a temporarily arrested heart to facilitate insertion of the shunt 132 into the vessel. With the shunt partially within the vessel, the surgeon then removes intravascular catheter 111 from the vessel as illustrated by the proximally-pointing arrow in Figure 9. The shunt 132 is then fully inserted into the vessel (Figure 10). The luer adapter 137 can be used to connect the shunt 132 to IV tubing and the like to continue the administration of the pharmaceutical composition (s) described above (e. g., to deliver into the vessel the one or more periodic bolus infusions of carbachol or the continuous infusion of carbachol) to maintain ventricular asystole of the heart. The

surgeon can then graft to the right coronary artery 75 while the heart is intermittently arrested (e. g., by selectively turning the pacer off and on) and while the shunt 132 is in place within the vessel. The shunt 132 provides distal perfusion to the vessel and prevents ischemia, while also maintaining a substantially blood-free zone in the surgical field.

With the shunt 132 in place within the vessel, the surgeon or surgeon's assistant then loosely places about five suture loops of 5/0 polypropylene, for example, around the "heel"of the graft vessel (e. g., an internal mammary artery or a saphenous vein) and passes the sutures through the wall of the coronary artery. The suture loops are pulled up to approximate the graft vessel to the coronary artery while leaving a sufficient space between the vessels to allow for removal of the shunt 132 from the coronary artery 75. For a more complete description of a typical distal anastomosis procedure, for example, the reader is referred to Doty, R. B. M. D., "CARDIAC SURGERY Operative Technique,"Ed. Mosby- Year Book, Inc., 1997, pp. 284-295, the entire contents of which are incorporated by reference herein. The surgeon or surgeon's assistant then removes the shunt 132 from the coronary artery 75 around the loose sutures and pulls the sutures tightly around the graft to give the graft a patent seal. The anastomosis procedure is completed using conventional techniques.

Turning the reader's attention now to Figures 11-15, two additional alternative embodiments of a fluid delivery device constructed in accordance with the principles of the present invention are disclosed. Both of the proceeding devices are provided with a fluid delivery member which is movably coupled to a support member, the support member being adapted to be secured proximate the vessel to assist in guiding the fluid delivery member into the vessel. Although the devices are generally more complex than the previously disclosed embodiments of the invention, the following devices have the advantage of providing the surgeon with greater control, stability, and precision during the insertion and placement of the fluid delivery member into the vessel.

According to the embodiment shown in Figures 11-13, a fluid delivery device 210 is shown. Fluid delivery device 210 generally includes an elongate tubular body, or extension tube, 212 having a proximal end portion 214, a distal end portion 216 having a distal opening 217 therein (see Figures 12 and 12A), and an axial lumen 218 (see Figure 12) between the proximal and distal ends of the tubular body 212. Preferably, the distal end of the tubular body 212 is slightly rounded (see Figure 12A) and soft to minimize

trauma to the vessel when the distal end is retained adjacent thereto as will be explained below.

Elongate tubular body 212 is integrally connected to a handle 220 at the proximal end of the tubular body 212. Handle 220 is configured to be grasped by the surgeon to allow the surgeon to grip and support the device 210 during placement of the fluid delivery member into the vessel as will be explained further below. Tubular body 212 is preferably a relatively rigid, plastic or metal tube having an outer diameter of between about 2 and 10 mm, and preferably between about 3 to 5 mm, so as to engage about the surface of a coronary vessel. Tubular body 212 is shown in the drawings as having a generally circular cross-sectional configuration. However, it is within the scope of the invention for tubular body 212 to have other configurations, including, but not limited to, square, rectangular, oval or channel or any other useful cross-sectional configuration. Tubular body 212 may also be curved or angled.

As shown in Figures 13 and 13A, a vacuum control assembly 240 is operably coupled to handle 220 and tubular body 212 for creating a suction holding force at the distal end opening 217 of the tubular body 212. The handle 220 is provided with an internal vacuum lumen 242 which connects the vacuum control device 244 to the tubular body lumen 218. The vacuum control device 244 is preferably a vacuum"on/off' mechanism, but may be any other equivalent mechanism that operates to selectively open and close the vacuum pathway provided by vacuum lumen 242. A CLIPPARD MINIMATICO three way poppet valve, Model No. MAV-3, Cincinnati, Ohio, is a preferred vacuum control device for use in the vacuum control assembly, and threadably engages with the handle 220. A vacuum hose 246 connects the vacuum control device 244 with an external vacuum source (not shown).

Vacuum applied from the vacuum source is then effectively applied at the distal end opening 217 of tubular body 212 via the pathway provided by components 246,244,242 and 218. In the application of the embodiment shown in Figure 11, the application of vacuum to the distal end opening 217 of the lumen 218 is initiated by pressing"on/off" button 241 of the vacuum control device 244, and discontinued by releasing the button.

Thus, the vacuum"on/off'button is operable to connect the vacuum conduit 242 to the vacuum source to create a suction force within tubular body lumen 218 when the button 241 is actuated by the practitioner, as will be explained in greater detail below. The suction force created within lumen 218 by actuation of vacuum"on/off'button 241 is sufficient to

trauma to the vessel when the distal end is retained adjacent thereto as will be explained below.

Elongate tubular body 212 is integrally connected to a handle 220 at the proximal end of the tubular body 212. Handle 220 is configured to be grasped by the surgeon to allow the surgeon to grip and support the device 210 during placement of the fluid delivery member into the vessel as will be explained further below. Tubular body 212 is preferably a relatively rigid, plastic or metal tube having an outer diameter of between about 2 and 10 mm, and preferably between about 3 to 5 mm, so as to engage about the surface of a coronary vessel. Tubular body 212 is shown in the drawings as having a generally circular cross-sectional configuration. However, it is within the scope of the invention for tubular body 212 to have other configurations, including, but not limited to, square, rectangular, oval or channel or any other useful cross-sectional configuration. Tubular body 212 may also be curved or angled.

As shown in Figures 13 and 13A, a vacuum control assembly 240 is operably coupled to handle 220 and tubular body 212 for creating a suction holding force at the distal end opening 217 of the tubular body 212. The handle 220 is provided with an internal vacuum lumen 242 which connects the vacuum control device 244 to the tubular body lumen 218. The vacuum control device 244 is preferably a vacuum"on/off' mechanism, but may be any other equivalent mechanism that operates to selectively open and close the vacuum pathway provided by vacuum lumen 242. A CLIPPARD MINIMATICO three way poppet valve, Model No. MAV-3, Cincinnati, Ohio, is a preferred vacuum control device for use in the vacuum control assembly, and threadably engages with the handle 220. A vacuum hose 246 connects the vacuum control device 244 with an external vacuum source (not shown).

Vacuum applied from the vacuum source is then effectively applied at the distal end opening 217 of tubular body 212 via the pathway provided by components 246,244,242 and 218. In the application of the embodiment shown in Figure 11, the application of vacuum to the distal end opening 217 of the lumen 218 is initiated by pressing"on/off" button 241 of the vacuum control device 244, and discontinued by releasing the button.

Thus, the vacuum"on/off'button is operable to connect the vacuum conduit 242 to the vacuum source to create a suction force within tubular body lumen 218 when the button 241 is actuated by the practitioner, as will be explained in greater detail below. The suction force created within lumen 218 by actuation of vacuum"on/off'button 241 is sufficient to

retain a surface of the vessel, such as the right coronary artery, adjacent (e. g., in contact with or near) the distal, open end opening 217 of tubular body 212 to facilitate insertion of fluid delivery member 230.

The fluid delivery device 210 also preferably includes at least one atraumatic tissue contact member 260 which can be used to help align the device with the longitudinal aspect of the vessel and/or stabilize a heart surface proximate the vessel (in lieu of suction force provided by vacuum control assembly 244). Preferably, the tissue contact member comprises a left foot 262 and a right foot 264 which are placed to straddle the vessel where fluid administration is to occur. The left and right feet 262,264 extend laterally from the distal end portion 216 of the tubular body and are arranged in a parallel orientation with one another. The lower surfaces of feet 262,264 may be substantially planar or slightly curved to conform to the shape of the heart and are adapted to make contact with a tissue surface of the heart about the vessel when in use with the vacuum to help align the device (e. g., the distal end of tubular body 212) with the vessel. Figure 12A is a bottom, perspective view of the distal portion of the device 210 giving another view of the feet 262, 264. The feet can be made from a biocompatible, non-toxic metal material such as stainless steel or a plastic material such as polycarbonate. Although the feet are shown fixed at the distal end of the tubular body 212, the feet 262,264 can also be arranged to swivel, or rotate, about the longitudinal axis of the tubular body 212 to add more flexibility to the distal end of the device to accommodate large variations in the relative position of the vessel relative to the surface of the heart. This may be important due to the large variances in vessel anatomy across a diverse patient population. Such rotation could be accomplished, for example, by coupling the feet to a locking ball joint (not shown) provided near the distal end portion of the tubular body 212 which is adapted for rotational movement. The locking ball joint allows the position of the tubular body 212 to be varied in any direction relative to feet 262,264. One example of such a locking ball joint configuration is fully disclosed in U. S. Patent No. 5,894,843, the entire contents of which are incorporated by reference herein.

With reference now to Figures 11 and 11 A, the device 210 further includes a fluid delivery member 230 which is configured to ride within a groove, or channel, 225 extending along a portion of the elongate tubular body 212. The fluid delivery member includes a main body portion 232 which is shaped to be conformably received within channel 225 and to be slidably moveable relative to channel 225. The main body portion is

retain a surface of the vessel, such as the right coronary artery, adjacent (e. g., in contact with or near) the distal, open end opening 217 of tubular body 212 to facilitate insertion of fluid delivery member 230.

The fluid delivery device 210 also preferably includes at least one atraumatic tissue contact member 260 which can be used to help align the device with the longitudinal aspect of the vessel and/or stabilize a heart surface proximate the vessel (in lieu of suction force provided by vacuum control assembly 244). Preferably, the tissue contact member comprises a left foot 262 and a right foot 264 which are placed to straddle the vessel where fluid administration is to occur. The left and right feet 262,264 extend laterally from the distal end portion 216 of the tubular body and are arranged in a parallel orientation with one another. The lower surfaces of feet 262,264 may be substantially planar or slightly curved to conform to the shape of the heart and are adapted to make contact with a tissue surface of the heart about the vessel when in use with the vacuum to help align the device (e. g., the distal end of tubular body 212) with the vessel. Figure 12A is a bottom, perspective view of the distal portion of the device 210 giving another view of the feet 262, 264. The feet can be made from a biocompatible, non-toxic metal material such as stainless steel or a plastic material such as polycarbonate. Although the feet are shown fixed at the distal end of the tubular body 212, the feet 262,264 can also be arranged to swivel, or rotate, about the longitudinal axis of the tubular body 212 to add more flexibility to the distal end of the device to accommodate large variations in the relative position of the vessel relative to the surface of the heart. This may be important due to the large variances in vessel anatomy across a diverse patient population. Such rotation could be accomplished, for example, by coupling the feet to a locking ball joint (not shown) provided near the distal end portion of the tubular body 212 which is adapted for rotational movement. The locking ball joint allows the position of the tubular body 212 to be varied in any direction relative to feet 262,264. One example of such a locking ball joint configuration is fully disclosed in U. S. Patent No. 5,894,843, the entire contents of which are incorporated by reference herein.

With reference now to Figures 11 and 11 A, the device 210 further includes a fluid delivery member 230 which is configured to ride within a groove, or channel, 225 extending along a portion of the elongate tubular body 212. The fluid delivery member includes a main body portion 232 which is shaped to be conformably received within channel 225 and to be slidably moveable relative to channel 225. The main body portion is

removably secured to channel 225 in a first position of the fluid delivery member 230 (e. g., when the fluid delivery member 230 is located external to the vessel) by a press-fit or interference-fit relationship. The fluid delivery member 230 generally includes a needle insertion assembly 234 which includes a proximal needle hub 235 which is connected to a flexible needle wire 236, such as a Nitinol needle wire, for example, to allow the needle to assume a pre-treated curved configuration conforming to the general curvature of the body portion 232. Such a shape can be easily generated by shaping the shape-memory Nitinol wire into the desired configuration and heat-treating the wire in that configuration, e. g., heating the wire beyond a specific"memory temperature"to give the wire a memory capability for this shape.

The distal end 238 of the wire 236 is beveled to create a sharp vessel penetration tip which can be used to puncture the vessel to insert the cannula portion 233 of fluid delivery member 230 into the vessel. The configuration of cannula portion 233 is generally similar to the configuration of the cannula portion 20 of device 10. The fluid delivery member 230 also includes a pair of suture wings 239 extending laterally from the body portion 232 which each include one or more suture holes 231 through which a suture can be tied to secure the fluid delivery member 230 proximate the vessel prior to fluid or drug administration therethrough.

To operate the device 210, the patient is prepared for surgery in a similar fashion as described above in relation to the previous embodiments. Following selection of the optimal target location for drug delivery along the length of the vessel, such as the right coronary artery 75, the surgeon prepares the target location on the right coronary artery by removing fat tissue and the like to expose the external surface of the vessel. With the right coronary artery partially exposed in the target region, the surgeon places the device 210 proximate the vessel such that the alignment feet 262,264 straddle the vessel to provide a visual reference location on the heart to aid in the precise positioning of the fluid delivery member 230 into the vessel. The surgeon then actuates the suction force by pushing on button 241 to enhance the securement of the device proximate to the surface of the vessel.

With the tissue surface on the vessel adequately stabilized, the operating surgeon or surgeon's assistant can then slide fluid delivery member 230 axially relative to tubular body 212 distally towards the vessel until needle 238 makes a small puncture, or opening, in the vessel. The cannula portion 233 of the fluid delivery member 230 is then advanced a short distance into the artery, and then the elongate tubular body 212 separated therefrom

and removed from the surgical field. With the cannula portion 233 partially in the vessel, the surgeon then removes needle insertion assembly 234 proximally away from the vessel.

Additionally, the surgeon may now thread one or more sutures through the suture hole (s) 231 provided in suture wings 239 and into the heart tissue to secure the fluid delivery member 230 proximate the vessel. A fluid or drug, such as a cardioplegia agent, may then be administered by connecting the hub of body portion 232 of the fluid delivery member 230 to IV tubing or the like in a similar fashion as described above in connection with the previous embodiments. The procedure then continues in a similar fashion as previously described and is not further described for convenience.

Turning now to Figures 14-15, an alternative embodiment of the invention is shown and generally indicated with the reference numeral 310. Device 310 is similar to the previous embodiment in that it also includes a support or stabilizing member operatively coupled to the fluid delivery device which securely retains a fluid delivery member at a desired location proximate the vessel to allow for easy insertion of the device into the vessel. However, unlike the previous embodiment, device 310 also includes actuators to allow the practitioner to accurately control the incident angle of insertion and the penetration depth of the fluid delivery member into the vessel. This may be important to provide the practitioner with greater control over the fluid delivery member to prevent the needle or the fluid delivery portion of the fluid delivery member from inadvertently piercing through the wall of the target vessel opposite the insertion site.

Specifically, the device 310 generally includes a fluid delivery member 320 which is operatively coupled to a support member 330. Fluid delivery member 320 can have a similar configuration to the fluid delivery member 230 described above. Alternatively, fluid delivery member 320 can be, for example, a 24 gauge Insyte-WO IV catheter available from Becton-Dickinson (Sandy, Utah) or other similar commercially available IV infusion catheter. Very generally, fluid delivery member 320 includes a cannula portion 322 (which can be similar to any of the cannula portions described previously), a needle insertion assembly (not shown), a main body portion 321, laterally extending suture wings 326 (having one or more suture holes 327 therein), and hub portion 328.

Support member 330 generally comprises a generally rectangular housing 332 and a generally rigid anchoring base portion 334 rotatably coupled to the housing 332. The base portion 334 is configured to secure the device proximate to the vessel insertion site. Base portion 334 is made from a suitable plastic material such as polyurethane and has a

generally flat bottom surface to prevent abrasion to the vessel and/or tissue surface proximate the vessel when it is secured thereto. The base portion 334 could also have a smooth, generally convex configuration to better conform the base portion to the contoured surface of the heart. The base portion could also include one or more laterally extending flanges (not shown) which can include one or more suture holes therein to allow the base portion to be stably sutured to a tissue surface of the heart proximate the intended target vessel. In addition, other means to secure the base portion 334 proximate the vessel can be employed as well, such as, for example, applying an adhesive to the lower surface of the base portion, such as cyanoacrylate, e. g., Loctite0, manufactured by Loctite Corporation (Hartford, CT) or applying a self-adhesive backing to the base portion to secure it to the heart, such as described previously. Where an adhesive material is used, the adhesive should preferably be compatible with biological tissue surfaces and the like and should be capable of easily being flaked off of the tissue surface following removal of the device therefrom.

Alternatively, the base portion 334 could also be configured to include a suction capability to enhance securement of the base portion proximate the vessel. For example, the base portion 334 could include one or more suction holes (not shown) through its bottom surface which fluidly communicate with a suction channel through a portion of the base portion. The suction channel in turn would communicate with a vacuum source which would be operatively coupled to the base portion 334 to effect a suction force at the bottom surface.

The base portion 334 is rotatably coupled to housing 332 via a rotatable knob 335.

Rotatable knob 335 in turn is fixedly attached to a rigid bar member (not shown for clarity) which is rotatably coupled to base portion 334 (base portion 334 acts as a bearing member to allow the bar member and knob 335 to rotate with respect to the base portion) and which is rigidly attached to a lower portion of housing 332 (e. g., by a press-fit or interference fit relationship). Accordingly, rotation of housing 332 relative to base portion 334 upon manipulation of knob 335 changes the incident angle of insertion of the cannula portion 322 of the fluid delivery member 320. The housing 332 and/or base portion 334 may include indicia (not shown) which indicate the particular incident angle of the fluid delivery member 320 relative to the vessel insertion site based on rotation of knob 335. Thus, the housing 332 can be rotated to any number of positions to suit a variety of particular applications.

generally flat bottom surface to prevent abrasion to the vessel and/or tissue surface proximate the vessel when it is secured thereto. The base portion 334 could also have a smooth, generally convex configuration to better conform the base portion to the contoured surface of the heart. The base portion could also include one or more laterally extending flanges (not shown) which can include one or more suture holes therein to allow the base portion to be stably sutured to a tissue surface of the heart proximate the intended target vessel. In addition, other means to secure the base portion 334 proximate the vessel can be employed as well, such as, for example, applying an adhesive to the lower surface of the base portion, such as cyanoacrylate, e. g., Loctite0, manufactured by Loctite Corporation (Hartford, CT) or applying a self-adhesive backing to the base portion to secure it to the heart, such as described previously. Where an adhesive material is used, the adhesive should preferably be compatible with biological tissue surfaces and the like and should be capable of easily being flaked off of the tissue surface following removal of the device therefrom.

Alternatively, the base portion 334 could also be configured to include a suction capability to enhance securement of the base portion proximate the vessel. For example, the base portion 334 could include one or more suction holes (not shown) through its bottom surface which fluidly communicate with a suction channel through a portion of the base portion. The suction channel in turn would communicate with a vacuum source which would be operatively coupled to the base portion 334 to effect a suction force at the bottom surface.

The base portion 334 is rotatably coupled to housing 332 via a rotatable knob 335.

Rotatable knob 335 in turn is fixedly attached to a rigid bar member (not shown for clarity) which is rotatably coupled to base portion 334 (base portion 334 acts as a bearing member to allow the bar member and knob 335 to rotate with respect to the base portion) and which is rigidly attached to a lower portion of housing 332 (e. g., by a press-fit or interference fit relationship). Accordingly, rotation of housing 332 relative to base portion 334 upon manipulation of knob 335 changes the incident angle of insertion of the cannula portion 322 of the fluid delivery member 320. The housing 332 and/or base portion 334 may include indicia (not shown) which indicate the particular incident angle of the fluid delivery member 320 relative to the vessel insertion site based on rotation of knob 335. Thus, the housing 332 can be rotated to any number of positions to suit a variety of particular applications.

The housing also preferably includes an actuator 340 which can be manipulated by the practitioner to accurately control the depth at which the needle insertion assembly portion of fluid delivery member 320 is inserted into the vessel. As best seen in Figure 15C, actuator 340 includes a threaded rod 342 which extends lengthwise along the vertical dimension of housing 332 through a cut-out portion 343 of the housing. An annular actuation ring 344 is threadably coupled to rod 342. Actuator 340 also includes a bracket 346 which rigidly secures the fluid delivery member 320 to the actuation ring 344. The main body portion 321 of the fluid delivery member 320 is configured to mate with the bracket 346 in a snap-fit or slight interference-fit relationship to rigidly secure the fluid delivery member 320 to the bracket, and also allow the fluid delivery member 320 to be easily separated from the bracket following insertion of the cannula portion of the fluid delivery member into the vessel. In turn, the bracket 346 may be rigidly secured to the actuation ring 344 by any suitable means such as by welding or brazing. The thread form relationship between actuation ring 344 and rod 342 means that rotation of actuation ring 344 will translate into axial, linear movement of fluid delivery member 320. A pair of slots 348 are formed in either side of housing 332 to permit passage of the bracket 346 vertically through the housing 332. In this way, linear movement of fluid delivery member 320 into the vessel can be accurately controlled to prevent piercing or trauma to the backside of the vessel during device insertion. Once the cannula portion 322 of fluid delivery member 320 is at least partially inserted into the vessel, the fluid delivery member 320 can be separated from bracket 346 and the support member 330 discarded. The fluid delivery member may then be sutured proximate the vessel using suture wings 326. The housing 332 can include indicia 350 on the sides of the housing to indicate the particular vertical orientation of the fluid delivery member 320 relative to the vessel insertion site.

Although the devices 210 and 310 described above are assembled such that the fluid delivery member is removably coupled to the support member, it is contemplated that the fluid delivery member also could be de-coupled from the support member and provided or packaged as a separate part from the support member. In this way, the support member could be first secured to a tissue surface near to or on the vessel proximate the device insertion site, and then the fluid delivery member could be coupled to the support member.

Movement of the fluid delivery member relative to the support member could then be accomplished by any of the previously described structures to facilitate insertion of the fluid delivery member (or a portion thereof) into the vessel.

The housing also preferably includes an actuator 340 which can be manipulated by the practitioner to accurately control the depth at which the needle insertion assembly portion of fluid delivery member 320 is inserted into the vessel. As best seen in Figure 15C, actuator 340 includes a threaded rod 342 which extends lengthwise along the vertical dimension of housing 332 through a cut-out portion 343 of the housing. An annular actuation ring 344 is threadably coupled to rod 342. Actuator 340 also includes a bracket 346 which rigidly secures the fluid delivery member 320 to the actuation ring 344. The main body portion 321 of the fluid delivery member 320 is configured to mate with the bracket 346 in a snap-fit or slight interference-fit relationship to rigidly secure the fluid delivery member 320 to the bracket, and also allow the fluid delivery member 320 to be easily separated from the bracket following insertion of the cannula portion of the fluid delivery member into the vessel. In turn, the bracket 346 may be rigidly secured to the actuation ring 344 by any suitable means such as by welding or brazing. The thread form relationship between actuation ring 344 and rod 342 means that rotation of actuation ring 344 will translate into axial, linear movement of fluid delivery member 320. A pair of slots 348 are formed in either side of housing 332 to permit passage of the bracket 346 vertically through the housing 332. In this way, linear movement of fluid delivery member 320 into the vessel can be accurately controlled to prevent piercing or trauma to the backside of the vessel during device insertion. Once the cannula portion 322 of fluid delivery member 320 is at least partially inserted into the vessel, the fluid delivery member 320 can be separated from bracket 346 and the support member 330 discarded. The fluid delivery member may then be sutured proximate the vessel using suture wings 326. The housing 332 can include indicia 350 on the sides of the housing to indicate the particular vertical orientation of the fluid delivery member 320 relative to the vessel insertion site.

Although the devices 210 and 310 described above are assembled such that the fluid delivery member is removably coupled to the support member, it is contemplated that the fluid delivery member also could be de-coupled from the support member and provided or packaged as a separate part from the support member. In this way, the support member could be first secured to a tissue surface near to or on the vessel proximate the device insertion site, and then the fluid delivery member could be coupled to the support member.

Movement of the fluid delivery member relative to the support member could then be accomplished by any of the previously described structures to facilitate insertion of the fluid delivery member (or a portion thereof) into the vessel.

All references cited herein are hereby expressly incorporated by reference.

The above is a detailed description of one or more particular embodiments of the invention. It is recognized and understood that departures from the disclosed embodiments may be made within the scope of the invention and that obvious modifications will occur to a person of ordinary skill in the art. For example, the device 10 of the first embodiment of the invention can also include a shunt coupled to the cannula portion 20 of the device similar to the configuration of the device 110. The shunt may be secured to the cannula portion 20 by removably securing a portion of the shunt to connector 30. A portion of the connector 30 could be configured to be broken away from or separated from the remaining portion of the connector 30 to allow the shunt to be separated therefrom and inserted into the vessel. The full scope of the invention is set out in the claims that follow and their equivalents. Accordingly, the claims and specification should not be construed to unduly narrow the full scope of protection to which the invention is entitled.